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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Near guideline study, GLP status not known, animal experimental study, minor restrictions in design and/or reporting but otherwise adequate for assessment.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPP 83-3 (Prenatal Developmental Toxicity Study)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Source: MC/B, 2909 Highland Ave., Norwood, Ohio 45212, USA
- Catalogue number: TX310
- Analysis: Performed with a UC-W98 column. Retention time was 1.9 minutes. Trace impurities noted at approximately 1.5 minutes and 2.1 minutes. - Purity appeared to be 98 to 99%, consistent with the MC/B assay of 99.79%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: CRL:COBS(SD)BR
- Source: Charles River Breeding Laboratories, Inc., Portage, Michigan, USA
- Age at start of treatment: 11 weeks
- Housing: Individually housed in wire cages
- Diet: Purina Laboratory Chow ad libitum
- Water: acidified pH 2.5 ad libitum
- Acclimation period: 12 days prior to pairing for mating

ENVIRONMENTAL CONDITIONS
- Temperature controlled: no data
- Humidity: no data
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: feed
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): no data
- Mixing appropriate amounts with (Type of food): DCPD was suspended in 300 mL of corn oil and blended with 10 kg of the basal diet in a twin shell blender for 15 minutes
- The control diet contained 300 mL of corn oil per 10 kg of meal
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Females were acclimated to laboratory conditions for 12 days and then paired with a sexually mature male of the same strain and from the same supplier
- Proof of pregnancy: Females were examined daily for the presence of a copulatory plug as evidence of mating, designated Day 0 of gestation
Duration of treatment / exposure:
Days 6-15 of gestation
Frequency of treatment:
Daily
Duration of test:
Days 0-19 of gestation
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 80, 250, 750 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
20 females
Control animals:
yes

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: The mated female rats were observed daily for changes in general appearance, behaviour and condition

BODY WEIGHT: Yes
- Time schedule for examinations: The mated female rats were weighed on Days 0, 6, 16 and 19 of gestation

FOOD CONSUMPTION: Yes
- Food consumption was measured during the period 0-6, 6-16 and 16-19 days of gestation

POST-MORTEM EXAMINATIONS: Yes
- On Day 19 of gestation the female rats were necropsied
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
- The number of implantation sites and their placement in the uterine horns, live and dead foetuses and resorption sites were recorded
Fetal examinations:
- External examinations: Yes: The foetuses were removed, examined externally for abnormalities and weighed.
- Soft tissue examinations: Yes: One third of the foetuses of each litter were fixed in Bouin's fluid. These were later examined for changes in the soft tissues of the head, thoracic and visceral organs.
- Skeletal examinations: Yes: The remaining foetuses of each litter were examined for skeletal abnormalities following staining with Alizarin Red S.
Statistics:
Statistical analysis of the data was performed using the litter as a basic sampling unit. Dunnett's t-test was used to determine statistical significance (p<0.05) with regard to difference between means with near normal distribution (maternal body weights and food consumption, mean pup weight based on litter averages). Ratios, e.g. sex ratio and pregnancy ratio, were analysed with a 2x2 contingency table with Yates' correction. With regard to discontinuous parameters as measured by the number of abnormal foetuses within a litter, Wilcoxon Rank Sum was used.

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:
750 ppm (nominal)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
750 ppm (nominal)
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

750 ppm equivalent to 60 mg/kg/day based on a 250 g rat consuming 20 g diet/day.

Applicant's summary and conclusion

Conclusions:
THE NOAEL for maternal and developmental toxicity was 750 ppm
Executive summary:

Administration of DCPD by incorporation into the diet at 80, 250 and 750 ppm produced no effect on pregnant dams when fed on days 6-15 of gestation. There was no evidence of teratogenicity or developmental toxicity at this dose.