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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Study was conducted prior to the advent of GLP regulations (1982)

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1967
Report date:
1967
Reference Type:
study report
Title:
Unnamed
Year:
1967
Report date:
1967
Reference Type:
secondary source
Title:
Unnamed
Year:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents)
Deviations:
yes
Remarks:
lesser haematological and clinical parameters have been investigated and no urinalysis was conducted; only 2 animals/dose/sex tested
Principles of method if other than guideline:
Groups of male and female Beagle dogs (2/sex/group) were maintained for 97 days on a diet containing 0.06, 0.2, or 0.4 % HEA in diet (equivalent to doses of 21, 60 and 125 and 22, 63 and 131 mg/kg body weight/day for males and females respectively).
GLP compliance:
no
Remarks:
(Study was conducted prior to the advent of GLP regulations)
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-hydroxyethyl acrylate
EC Number:
212-454-9
EC Name:
2-hydroxyethyl acrylate
Cas Number:
818-61-1
Molecular formula:
C5H8O3
IUPAC Name:
2-hydroxyethyl acrylate
Test material form:
not specified
Details on test material:
not specified
Specific details on test material used for the study:
- Analytical purity: 97 %
- Source: Texas Division
- Physical state: pale yellow liquid
- Density: ca. 1.07

Test animals

Species:
dog
Strain:
Beagle
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6-7 months
- Weight at study initiation: no data
- Housing: 2 dogs/cage
- Diet (ad libitum): Purina Laboratory Chow mixed with 1 % peanut oil
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
no details

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
97 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
21 mg/kg bw/day (nominal)
Remarks:
administered in males
Dose / conc.:
60 mg/kg bw/day (nominal)
Remarks:
administered in males
Dose / conc.:
125 mg/kg bw/day (nominal)
Remarks:
administered in males
Dose / conc.:
22 mg/kg bw/day (nominal)
Remarks:
administered in females
Dose / conc.:
63 mg/kg bw/day (nominal)
Remarks:
administered in females
Dose / conc.:
131 mg/kg bw/day (nominal)
Remarks:
administered in females
No. of animals per sex per dose:
2
Control animals:
yes, plain diet
Details on study design:
Post-exposure period: no
Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: frequently

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: frequently

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
- Food consumption records were kept weekly throughout the experimental period

HAEMATOLOGY: Yes
- Time schedule for collection of blood: before test start and after 83 days on the diet
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: all
- Parameters examined: hematocrit, RBC, hemoglobin, WBC, differential count

CLINICAL CHEMISTRY: Yes
- How many animals: all
- Parameters examined: serum urea nitrogen, alkaline phosphatase, bromsulfophthalein (B.S.P.), serum glutamic oxalacetic transaminase (S.G.O.T.), and serum glutamic pyruvic transaminase (S.G.P.T.) values

URINALYSIS: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

All animals were fasted overnight and weighed before examination at autopsy. Bone marrow smears were taken from the rib of the male and female dogs on the control and 0.4 percent levels of 2-hydroxyethyl acrylate and from the female dogs on the control. The lungs, heart, liver, kidneys, spleen, brain, and testes were removed and weighed.
Portions of each organ, as well as lymph node, esophagus, aorta, pancreas, uterus, ovary, urinary bladder, gall bladder, stomach, skeletal muscle, large intestine, small intestine, spinal cord, pituitary gland, adrenal gland, thyroid, parathyroid, and peripheral nerve were preserved. Hematoxylin-eosin stained sections of the tissues were prepared for microscopic examination.
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No compound-related effects
Mortality:
no mortality observed
Description (incidence):
No compound-related effects
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Further details / tables see attachments.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No compound-related effects

Further details / tables see attachments.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
No compound-related effects

Further details / tables see attachments.
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No compound-related effects

Further details / tables see attachments.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No compound-related effects

Further details / tables see attachments.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No compound-related effects

Further details / tables see attachments.
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
No compound-related effects

Further details / tables see attachments.

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
125 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: high dose
Key result
Dose descriptor:
NOAEL
Effect level:
131 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: high dose

Target system / organ toxicity

Key result
Critical effects observed:
no

Any other information on results incl. tables

One female dog on the 0.4 percent level of 2 -hydroxyethyl acrylate was relatively small at the beginning of the experimental period and showed a slight weight loss during this period. This dog was found to have an enlarged spleen. However, upon microscopic examination of the tissues from this animal, no evidence of adverse changes was noted. Thus, the dog's condition was not attributed to the experimental compound.

 

Thus, there was no evidence of adverse effects as judged by general appearance and behavior, weight gain, food consumption, hematological values, examination of bone marrow, urea nitrogen content and alkaline phosphatase activity in the serum, serum bromsulfophthalein, serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase tests, final average body and organ weights, and gross and microscopic examination of tissues.

Details on hematology, clinical chemistry, body weight, organ weights and pathological/microscopic examinations are given in the attachment.

Applicant's summary and conclusion