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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 06 Jan. 2004 to 1 Feb. 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Data generated according to international accepted valid testing method

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD 422 Guideline for testing of chemicals
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Huntingdon Life Sciences, Wooley Road, Alconbury, Huntingdon, Cambridgeshire, PE284HS, England
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test substance was Glyoxylic acid 50 (a 50% w/w solution of glyoxylic acid in water) which was incorporated into the diet of CD rats.
Storage conditions: at ambient temperature or in a refrigerator, unless otherwise directed by the Sponsor.

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Details on test animals and environmental conditions:
Species: Rat
Strain: Crl:CD (SD) IGS BR
Age ordered: 7 weeks of age males and females not siblings
Weight range ordered: To be within an 15 g range for each sex/batch
Supplier: Charles River (UK) Limited
Acclimatisation:
Duration: At least 5 days before commencement of treatment.

Animal - housing, diet and water supply:
Rodent facility: Full barrier - to minimise entry of external biological and chemical agents.
Air supply: Filtered, not recirculated.
Temperature: Maintened within the range of 19-23°C.
Relative humidity: Maintened within the range of 40-70%
Lighting: 12 hours light: 12 hours dark.

Animal accomodation:
Animal per cage: Males and females housed in mating pairs during mating, males then returned to group housing, females then remain singly housed.
Cage material: Polypropylene or stainless steel.

Diet name: SDS VFR 1 Certified
Diet type: Powdered diet.
These diets contain no added antibiotic or other chemotherapeutic or prophylactic agent.

Water supply: Potable water from the public supply.

Administration / exposure

Route of administration:
oral: feed
Details on exposure:
Continuously from 14 days before pairing, during 14-day pairing period, gestation, littering and lactation period until day 4.
Analytical verification of doses or concentrations:
yes
Details on mating procedure:
All 10 males in each group (toxicity and reproductive subgroups) were paired with the 10 reproductive subgroup females after all animals had received 2 weeks of treatment.
Pairing was on a one-to-one basis within treatment groups; up to 2 week was allowed although all animals mated and were separated within 1 week.
From day 20 after mating reproductive subgroup animals were checked 3 times daily for evidence of parturition.
The female were permitted to deliver their young naturally and rear their own offspring until Day 4 of lactation.
Numbers of live and dead offspring were recorded during the parturition process.
All offspring were examined at approximately 24 hours after birth (Day 1) and the number of offspring born (live and dead) was recorded.
Litters were observed daily for evidence of abnormal appearance or behaviour. Daily records were maintained for mortality and consequent changes in litter size.
Reproductive subgroup males were killed during Week 6 of treatment.
Reproductive subgroup females and their offspring were killed on Day 4 of lactation/age (during Weeks 6 or 7 of treatment for the females).
Frequency of treatment:
Daily in the diet
Duration of test:
Approximately 8 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 2000, 6000 and 18000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
Four groups of 5 males and 10 females per group
Control animals:
yes

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
18 000 ppm
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
18 000 ppm
Based on:
test mat.
Basis for effect level:
other: other

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
18 000 ppm (nominal)
Based on:
test mat.
Basis for effect level:
other: screening observation

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Treatment at all dietary concentrations was well tolerated and there were no mortalities.

Bodyweight gain and food intake of reproductive subgroup females during gestation and early lactation was unaffected by treatment.

Achieved dosages for females at the start of gestation (Days 0-7) were 97, 296 and 910 mg/kg/day for females in the 2000, 6000 and 18000 ppm groups.

Achieved dosages during Days 1-4 of lactation were about 49-56 % higher (126, 383 and 1257 mg/kg/day respectively) than those at the end of gestation, reflecting increased physiological demand on the dams by the litters.

Achieved dosages largely reflected the three-fold difference in dietary concentrations of Glyoxylic acid 50.

There was no effect of treatment on the sensory reactivity, grip strength or motor activity of the animals monitored during Week 5.

Mating performance and fertility were unaffected by treatment.

Parental treatment had no effect on the survival, growth or development of the offspring or absolute or bodyweight relative organ weights.

There were no microscopic pathology changes in the tissues examined that were considered to be related to treatment.

Applicant's summary and conclusion

Conclusions:
Based on the results of this study, it was concluded that the NOAEL for reproductive/developmental toxicity within the scope of this screening test was 18000 ppm.

The study was considered to have met the objectives of the OECD Guideline 422.

The reproduction/developmental toxicity screening test found no evidence of impaired performance at these dietary concentrations.