J Basic Clin Physiol Pharmacol 2018; aop
Review
Sulagna Dutta and Pallav Sengupta*
Rabbits and men: relating their ages
https://doi.org/10.1515/jbcpp-2018-0002
Received January 5, 2018; accepted February 16, 2018
Abstract: Rabbit, a member of the Lagomorpha order, is
the closest phylogenetic relative to humans, next to pri-
mates. It possesses greater acceptability as a laboratory
mammal than primates in terms of husbandry, breeding
ease, cost effectiveness, and legal ethical conveniences.
Moreover, as a laboratory animal, the rabbit also owns
its advantages over mice or rats, in terms of phylogenetic
resemblance to human, size, blood volume, responsive-
ness, and other congruences enabling them to better
imitate human physiological characteristics in biomedi-
cal research. A specific research aspires to effectuate its
outcome on a particular human age group, for which it
is pivotal to select a laboratory rabbit of exact age, which
will correlate with that specific age of a human, which
is currently based on mere approximation. This article
is the first ever scientific venture, focused to swap this
approximation of laboratory rabbit age with accuracy by
relating it with that of humans analyzing different phases
of life individually. Considering the diminutive lifespan
of rabbits compared to humans, the correlation of their
age with respect to the entire lifespan, which we found
out to be 45.625 days compared to one human year, is not
enough. Thereby, like our previous articles that formu-
lated concise relation of age of laboratory rats and mice
with human age, in this article also, we aim to aid bio-
medical research specificity in the selection of laboratory
model age, separately correlating different life phases
of humans with that of rabbits, the second mostly used
mammal in 2016 in the United States.
Keywords: developmental biology; human age; laboratory
rabbit; physiology; rabbit age.
*Corresponding author: Pallav Sengupta, Ph.D., Department of
Physiology, Faculty of Medicine, MAHSA University, Jalan SP2,
Saujana Putra, 42610 Selangor, Malaysia, Phone: +60 17 4523 780,
E-mail: pallav_cu@yahoo.com, http://orcid.org/0000-0002-1928-5048
Sulagna Dutta: Department of Physiology, Faculty of Medicine,
MAHSA University, Saujana Putra, Selangor, Malaysia
Introduction
The quintessential first step to proceed toward most of
the in vivo biomedical appraisals is the selection of an
appropriate animal model that can mimic the physiologi-
cal attributes of human beings to the maximum possible
extent. The research conducted using the chosen animal
model should procure information approximating the
expectations of the same in human beings [1]. It becomes
almost unfeasible to recruit large mammals, like monkeys
and dogs in research requiring rigorous repetitive experi-
ments for which the number of animals needed is huge
and immensely expensive. The prodigious sacrifice of
large mammals is against legal as well as humane ethics.
Next to the primates, Lagomorphs bear the closest phylo-
genetic relationship with human beings, and among the
lagomorphs, rabbits stand at the closest trunk of resem-
blance to human phylogeny [2]. They are also genetically
closer to humans than rodents [3]. Rabbits belong to the
family of Leporidae of the order Lagomorpha [4]. Taxono-
mists have determined that there are 47 distinct species
of rabbits [5], while the American Rabbit Breeders Asso-
ciation (ARBA) has currently recognized 49 unique rabbit
breeds [6]. Among these, the New Zealand White (NZW)
strains of rabbits (Oryctolaguscuniculus) are mostly being
utilized for biomedical research activities [7].
We have reported in our previous article [8], based on
the data of the European Union (2010), that among the
worldwide animal usage, rabbits (3%) were the third most
used laboratory mammals after mice and rats. The United
States Department of Agriculture (USDA)/Animal and Plant
Health Inspection Service (APHIS) have also pointed out a
declining trend of rabbit usage from 1950 to 2010 [9]. They
have informed similar declining patterns of use of rabbit
for research from 1973 to 2015 [10–12]. This decrease in the
laboratory use of rabbit in the said phase may be the con-
sequence of the strong global protest against animal usage
for experimentation, its experimental cost, the stoppage of
using rabbits for cosmetics, the development of new trans-
genic technologies for mice and rats, and/or diverting the
biomedical research toward in vitro experimentations. This
is also evident from the data of USDA/APHIS showing an
8% decline in the overall use of all animals for research
from 2014 to 2016 [13–15]. For the same reason, the number
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2      Dutta and Sengupta: Rabbit age versus human age
of laboratory rabbits used in 2000  has been 258,754,
whereas in 2016, the number is 139,391 [13]. Despite such
restrains on the allocation of the number of rabbits for
research by the Ethical Committees globally, this mammal
is indispensable for several biomedical research interven-
tions. The vitality of laboratory use of rabbits is evident
from the USDA/APHIS showing that, in 2016, rabbits stood
at rank second among the most used animals in research,
teaching, and testing in the US, after an 8% increase in
their usage from the previous year [13] (Figure 1).
The characteristics of laboratory rabbits such as its
cost effectiveness, husbandry ease, availability, ability of
frequent breeding yielding large litter sizes, and conveni-
ence to be used in versatile research match the advantage
criteria of mice and rats, whereas its high blood volume,
more phylogenetic, hemodynamic, and histological
resemblance to humans attributed to its larger size match
the advantage criteria of large mammals, which mice and
rats are unable to serve [2]. They also possess short vital
cycles making it convenient to examine in a tinier span of
research time (Table 1). Moreover, they enable researchers
Figure 1: Phylogenetic proximity of rabbit to human and its research versatility increases the use of rabbit in the biological research.
(A) Phylogenetic position and research benefits of rabbits and (B) trend of total animal and rabbit use in biomedical research.
to standardize the environment according to the need of
the experiment, even permitting the genetic standardiza-
tion required for specific biomedical research [16].
In our earlier publications, we have correlated the age
of rats [8] and mice [17] with that of humans at different
stages of life. In this article, gauging the vitality of rabbits
in biomedical research, considering its advantages over
mice and rats, while matching the conveniences of the
same, urged us to correlate the age of laboratory rabbits
with that of humans at various developmental stages of
life in order to assist the researchers to select the labora-
tory rabbit of exact age correlating with the corresponding
age of humans on which the researchers aim to effectuate
their experiments without any loopholes in the biomedi-
cal research endeavors.
Laboratory rabbits: breeds and research uses
The order Lagomorpha contains rabbits, hares, cot-
tontails, and pikas. Common breeds of domestic and
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 Dutta and Sengupta: Rabbit age versus human age      3

Table 1: General physiology and reproductive data of laboratory rabbit (NZW).

Common physiological data Reproductive data

Chromosome number (2n) 44 Age at estrous 5–6 months

Birth weight 30–80 g Weight at estrous 1.7–3 kg
Adult weight 2–6 kg Frequency of estrous cycle Induced
Growth rate 15–20 g/day to 8 weeks Duration of estrous NA
Body temperature 38–40 °C Time of ovulation After mating
Body surface area 9.5 ×  (weight in grams)2/3 Menopause 5–7 years
Energy requirement for growth 180–200 kcal/day Parturition interval 79 days
Water consumption 100–600 mL/day Average sperm volume, mL 0.3–0.6
Food consumption 100–300 g/day Sperm concentration, ×106/mL 150–500
Skeletal weight 7–8% of total body weight Sperm motility, % ~60
Average litter size 4–10 Serum testosterone (ng/mL) 2.0–2.5
Heart rate 130–325 Time sperm detected in vagina 3–24 h
Arterial blood pressure
 Systolic 90–130 mmHg Time of implantation Days 8–9 of gestation
 Diastolic 60–90 mmHg Length of gestation, days 31–32
Respiratory rate 30–60 per min
Blood volume 45–75 mL/kg body weight

NA, not applicable; NZW, New Zealand White.

laboratory rabbits are all derived from the European
rabbit (Oryctolaguscuniculus) [7, 18]. The breeds most
commonly used for research include the NZW (albino),
Dutch-belted, Californian White, Polish, and New
Zealand Red [7]. Among 49 breeds, as discussed earlier,
approximately 30 breeds (along with mutant strains)
of rabbits have been recognized by ARBA for commer-
cial and research purposes [6, 7, 19]. Rabbit breeds vary
greatly in size and are often classed on the basis of body
weight as being small, less than 2 kg (Dutch, Polish);
medium, 2–5 kg (New Zealand and Californian); large,
greater than 5 kg (Flemish) [6]. The NZW (albino) is
the most widely used breed in laboratories. The major
advantageous feature of this breed is the ease of location
of surface veins and arteries (especially in the ear) for
blood collection [20, 21] (Table 2).
Rabbits are used for toxicity and safety testing of
numerous substances ranging from drugs, chemicals,
medical equipment (such as pyrogens, teratogens) to
substances of daily usage. The skin and eye irritation
experiments for testing several chemical hazards, such
as the archaic and painful Draize test, are performed
using rabbits [4] besides the several other potential
methods for the same [22]. Rabbits also serve as imita-
tion models to study several human diseases, such as
atherosclerosis [23], Alzheimer’s disease [24], AIDS
[25, 26], cancer [27, 28], reproductive and developmen-
tal ­toxicity [29], eye research [30], and other diseases
[4]. These mammals are also used as the medium for
­bioreactions to produce essential pharmaceutical pro-
teins [31]. They are universally and routinely used in
serology for polyclonal antibody production because of
the readiness with which they produce serum antibod-
ies evoked by a wide variety of antigenic stimuli and
owing to their higher blood volume compared to mice
and rats [2, 8, 17]. Apart from this, various implantation
research methodologies are based on this expedient
mammal [29].

Table 2: Commonly used breeds of laboratory rabbits and their research applications.

Mostly used breeds Ideal mature Average Duration of Research applications

weight, lb ( / ) litter size gestation, days

NZW (albino) 10/11 4–10 31–32 Cancer, infectious diseases, and other immunological research,
atherosclerosis and hypertension research, serological genetics,
metabolic research, and other diseases of public health significance
Dutch belted rabbits 2.5/2.5 5–6 30–33 Developmental toxicity studies, better model for glaucoma
Californian White 9/9.5 7–9 28–32 Virology research
Polish rabbits 2.5/2.5 2–4 28–34 Pharmacokinetics study, metabolic research
New Zealand Red 10/11 7–8 28–35 Tuberculosis, leprosy, mycobacterial, and infectious disease research

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4      Dutta and Sengupta: Rabbit age versus human age
Age determination of laboratory rabbits:
common methods
Several methods have been proposed for the determina-
tion of rabbit age since the 1940s. Southern [32] had first
reported that the body weight of a rabbit increases with
advancement of age up to 3–4 weeks, and it is a satisfac-
tory criterion for age determination in rabbits. In 1953,
Tyndale-Biscoe proposed the age determination method
by the sequential recording of the epiphyseal fusion of
bones. They pointed out that, in rabbits, the epiphy-
sis at the head of the tibia fuses at the 41st week (range
33–44 weeks) [33]. In another report, they confirmed that
the epiphyses of all other long bones unite at about the
same age or earlier than do those at the head of the tibia
[34]. Following these report, in 1959, Lord came up with
his pioneering report of age determination method by eye
lens weight [35], and since then, several methods have
been proposed for age determination in rabbits using ear
length [36], hindlimb length [37], the closure and thick-
ening of the humoral and ulnar epiphysis [37, 38], the
ossification of the skull and pelvis [37], annual layers of
mandibular bone [39], etc. Several reports also published
a comparative efficacy of two or more methods [36, 37].
However, most of these methods are reported to be relative
and alters their accuracy in different phases of life. It has
been suggested in a few studies that, to get the actual age
of a rabbit, researchers should compare at least two deter-
mination methods relevant to the study [36].
Eye lens weight
Lord [35], as discussed earlier, had put forth the concept of
estimating the age of rabbits on the basis of the dry weight
of the eye lens. He had given a formula [Age = 68.7927/
(2.4890 − log10 dry weight of lens) − 41]. Based on his
formula, Edwards [40] had constructed tables for esti-
mating rabbit ages and birth dates ‘with suggestions for
handling lenses’. These methods of determining age are
also relative and lose precision with advancing age, and
the standard curves vary with the population. Following
these reports, numerous studies have been published
indicating the advantages and disadvantages of the use of
dry lens weight as an indicator of rabbit age [38, 41, 42].
Musculoskeletal examination: epiphyseal closure
Following the experiments of Tyndale-Biscoe in 1953 [33],
Taylor demonstrated the method of measurement of age
in rabbits by tibial epiphyseal fusion [43]. They reported
that, in rabbits of less than 10 months old, proximal tibial
fusion remains absent; in rabbits of 10–25  months old,
fusion of tibia was found, but all the posterior epiphy-
ses of the lumbar vertebra remained unfused; in rabbits
of 26–33  months old, the posterior epiphysis of the 7th
lumbar vertebra was fused, but the posterior epiphyses of
the 6th lumbar vertebra were unfused; but in rabbits of
more than 33  months old, the posterior epiphysis of the
6th lumbar vertebra was fused [43]. They had claimed
that this method is reported to be useful in reproductive
[44] and microbiological (parasitic) research [45]. They
indicated that the major disadvantage of this process is
its application in living animals, but completely unfused
tibial epiphysis can be felt with the thumbnail, while the
unfused vertebral epiphysis cannot be detected easily,
even not by X-ray [43]. In humans, the epiphyses of the
bones of the upper part of the body are observed to close
at the age of 14–18 years, whereas that of the lower body
occurs at the age of 18–25 years. Bone remodeling and its
maintenance indicate the age of early adulthood, whereas
late adulthood is demarcated by analysis of bone wear
and tear. Epiphyseal evaluation demands detailed scru-
tiny of the skeletal remains as well as the radiological
assessment of the fleshed material [46].
Body weight assessment
It is important to determine the age of laboratory rabbits
and separate them into groups according to their age cat-
egories prior to experimentations. The most convenient
method to do so is by plotting the frequency distribution
of their body weights from which the different age classes
of the rabbits can be statistically determined [32]. The
approximate age of laboratory rabbits can also be ana-
lyzed by keen observation by their physical characteristics
during the first 4 weeks, since their birth to weaning [32]
(Figure 2).
Annual layers of mandibular bone
Determination of the annual layers in the dentine or
cementum is a useful tool in analyzing the age of carniv-
orous or hooved mammals. However, in the case of the
Lagomorpha, the incisors and lapsodont molars grow
continuously impeding the restoration of their annual
layers, if formed. Bernstein and Klevezal [47] had paved
the way to determine the age of the Lagomorpha using
adhesion lines, which are alike annual layers at the
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Figure 2: Physical and behavioral attributes of rabbits in different phases of life.
periosteal zone in the mandible and is formed in every
winter season. Some of the adhesion lines appear in the
rapid growth phase of the rabbit before the first winter
of the Lagomorpha’s life. Thus, by analyzing these adhe-
sion lines, one can determine the number of winters
passed by the rabbit and, hence, can interpret the age
[47]. Later, Ohtaishi et  al. in 1976 confirmed that this
method is more accurate than the other age determining
methods [39].
Relation between rabbit age and human age
In biomedical experiments with rabbits representing
humans, the rabbit age must be precisely determined in
relation to human age, in terms of both the lifespan and
individual life stages, to attain utmost accuracy and speci-
ficity in research. In the following section, we present
human age with that of the laboratory rabbit at different
developmental stages of life.
Relation between their lifespans
Rabbits have a shorter and accelerated early life, com-
pared with humans. Their lifespan is influenced by breed,
living conditions, and healthcare, but the average life
expectancy is about 8–12  years [48, 49]. However, in the
Dutta and Sengupta: Rabbit age versus human age      5
laboratory and breeding colony, it reduces due to the
strains in those particular environments [50]. As the devel-
opmental stages of rabbits are not uniform with those of
humans, the correlation between their entire lifespans
must not be determinant of the human days in terms of
rabbit days and vice versa, at every phase of life.
The average lifespan of a laboratory rabbit is about
10  years [49] (Table 1), whereas the life expectancy of
humans globally is about 80  years [51], which varies
among countries based on economic status[8].
Therefore, considering both lifespans, the correlation
can be calculated as follows:
(80 × 365) ÷ (10 × 365) = 8 human days = 1 rabbit day;
and
365 ÷ 8 = 45.625 rabbit days = 1 human year.
Thus, one human year is almost equivalent to 45.625
rabbit days when correlating their entire lifespan.
Weaning period of rabbits and humans
Mammals have an altruistic nature, and they nurse
and feed their young ones until they withdraw from
the mother’s milk and learn to survive independently.
‘Weaning is the transition of the human infant from
breast-feeding or bottle nursing and commencement
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6      Dutta and Sengupta: Rabbit age versus human age
of nourishment with other food’ [52]. After birth, baby
rabbits remain hairless with closed eyes. They generally
open their eyes around the 10th day (P10) [50]. Since
that time, they continue to nurse with their mother’s
very rich milk until weaning at around the 4th week
(P28), when they start to walk. Rabbits start taking solid
foods around P14 to P21 and reduce taking the mother’s
milk after P21. However, they generally kept with their
mother until P42, as separation from the mother at this
age may well lead to enteritis, which is usually fatal to
baby rabbits. During this phase they develop their teeth,
and male rabbits (bucks) are separated from females
(does) [48, 53].
Rabbits are weaned at 4–6 weeks, approximately on
the 28th day (P28), after birth. While weaned, the bunnies
become robust with completely developed teeth and fur,
able to jump, feed, and drink on their own [49]. On the
other hand, the average weaning age for humans is about
6 months (180 days) [8, 17].
Thus,
180 ÷ 28 = 6.43 human days = 1 rabbit day
and
365 ÷ 6.43 = 56.77 rabbit days = 1 human year.
Therefore, in this developmental phase, one human
year equals 56.77 rabbit days.
Rabbit and human age to attain puberty
Puberty is attained when maturation of the hypothalamo-
pituitary-gonadal axis reaches its peak, altering gonado-
tropin levels in circulation and shooting up the levels
of sex steroids. Bucks attain sexual maturity at around
3–5  months and doe rabbits a little later at around
5–6 months of age [53]. This reproductive change is nearly
always accompanied by a marked change in behavior.
Bucks become more aggressive and often spray urine as a
sign of courtship. Doe rabbits tend to become very territo-
rial over their personal space [50].
The average age at which rabbits attain puberty is
about 150 days (P150) [50], and the average age in humans
is about 11.5 years (11.5 × 365 = 4198 days) [8, 17].
Thus, in the prepubertal phase,
4198 ÷ 150 = 27.98 human days = 1 rabbit day,
and
365 ÷ 27.98 = 13.04 rabbit days = 1 human year.
Thus, in this phase, one human year is equivalent to
13.04 rabbit days.
Adulthood in rabbits and its relation to humans
Adulthood is the age of attainment of sexual maturity,
which is associated with distinct psychological and social
conceptions. Rabbits attain sexual maturity approxi-
mately at 1 year of age (P365) [50, 54]. Rabbits weigh about
50–70 g at birth, with the adult rabbit reaching 2–6 kg
(Figure 2). The adulthood in rabbits is generally classified
into three phases, young adults (1–3  years), middle age
(3–5 years), and late middle age (5–6 years). Young adult-
hood is the most active phase of a rabbit’s life followed
by middle age when the movements slow down gradually,
and in the late middle age, arthritis and other age-related
problems start to creep. In young adulthood, doe rabbits
initiate their estrous cycle. The rabbit does not have an
estrous cycle with a regular interval, so it may be consid-
ered as continuous [44, 53]. In this phase, the doe mounts
with the buck or another doe. Both of them remain fertile
in this phase. The number of eggs and sperms are highest
in this phase [55, 56]. In every year, October to December
is considered as the mounting season for rabbits [5]. Like
other mammals and humans, the epiphyseal growth plate
closure may be considered as one of the differentiators
between adolescence and adulthood in rabbits [57].
The last growth plates in the scapula of the human
fuse  at about 20  years of age on average (365 × 20 = 
7300 days) [57].
Therefore, from these data, it can be calculated that
7300 ÷ 365 = 20 human days = 1 rabbit day,
which indicates that
365 ÷ 20 = 18.25 rabbit days = 1 human year.
Thus, during the adult phase, 18.25 rabbit days are
equivalent to one human year.
Reproductive senescence in rabbits and humans
Although the biomarkers of aging are not very authentic
to detect reproductive senescence, in rabbits, reproduc-
tive functions cease in late middle age, which is con-
sidered to be around 6  years (P2190) [50]. In humans,
menopause in women is a marker of reproductive senes-
cence, which is associated with the termination of the
fertility cycle. The average age of menopause in women,
according to the American Medical Association, is 51 years
(51 × 365 = 18,615 days) [8].
Thus,
18,615 ÷ 2190 = 8.5 human days = 1 rabbit day,
and
365 ÷ 8.5 = 42.94 rabbit days = 1 human year.
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 Dutta and Sengupta: Rabbit age versus human age      7

Table 3: (A) Correlating one human year with rat days in different phases of life, and (B) comparing social maturity phases of humans and
rabbits.

(A) Correlating human years with rat days (B) Rabbit age versus human age

Rabbit age Human age

Entire life span 45.625 rabbit days =1 human year 3 weeks 4 years
Weaning period 56.77 rabbit days 1 month 6 years
Pubertal phase 13.04 rabbit days 3 months 10 years
Adulthood 18.25 rabbit days 4 months 12 years
Reproductive senescence 42.94 rabbit days 6 months 16 years
Post-senescence period 50.34 rabbit days 1 year 21 years
2 years 27 years
3 years 33 years
4 years 39 years
5 years 45 years
6 years 51 years
7 years 57 years
8 years 63 years
9 years 69 years
10 years 75 years

Figure 3: Mapping of rabbit age to human age in different life periods is vital for experimental research using rabbit model.
(A) The advantages of rabbit use in animal research over primates and small rodents, and (B) comparing rabbit and human ages in different
life periods.

Thus, during reproductive senescence, 42.94 rabbit humans may survive approximately for 10,585 days after
days are equivalent to one human year (Table 3). senescence [8].
Thus,

Post-senescence phase in rabbits and humans
If the periods of post-senescence to death are com-
pared, the following is found: rabbits live almost 4 years
(P1460) after reproductive senescence, and female
10,585 ÷ 1460 = 7.25 human days = 1 rabbit day,
365 ÷ 7.25 = 50.34 rabbit days = 1 human year.
Thus, in the senescence phase, 50.34 rabbit days are
equivalent to one human year (Figure 3).

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8      Dutta and Sengupta: Rabbit age versus human age
Conclusions
Traversing the disparity of a minute lifespan of a rabbit
compared to an elaborate one in the case of a human,
this article bridged rabbit age and human age stepping at
different life stages individually. Thus, the present com-
prehensive age correlation successfully constructs a firm
ground aiding accuracy in the first step of every arena of
biomedical research that uses rabbits as imitation models
of the humans, that is, to select a laboratory rabbit of
accurate age swapping the need of approximation.
Author contributions: All the authors have accepted
responsibility for the entire content of this submitted
manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played
no role in the study design; in the collection, analysis, and
interpretation of data; in the writing of the report; or in the
decision to submit the report for publication.
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