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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-designed study in a reputable corporate laboratory. Adequate detail is provided to assess the validity of the conclusions.
Justification for type of information:
Ethanedinitrile, hydrogen cyanide (HCN), potassium cyanide and sodium cyanide can be considered as a chemical category, along with and acetone cyanohydrin (ACH, also known as 2-hydroxy-2-methylpropanenitrile), based on structural similarity, common breakdown/metabolic products in physical and biological systems, and similar physico-chemical properties. Particular attention is paid to the dissociation constant of HCN. Ethanedinitrile breaks down in aqueous solution into cyanide ion (CN-) and cyanate ion (OCN-) (Cotton and Wilkinson 1980). Ethanedinitrile due to its low log Kow (0.07) and relatively high solubility in water (2.34 g/L) needs to get dissolved in aqueous solutions in lungs to enter the body. The rate of hydrolysis of ethanedinitrile is very fast (Ajwa 2015). Also, in the vast majority of environmental and physiologic conditions, the cyanide salts will dissolve in water to form hydrogen cyanide. The physico-chemical hazards and toxicity therefore result from the activity of HCN. An ECETOC Task Force, in the 2007 ECETOC Joint Assessment of Commodity Chemicals (JACC) Report No. 53, “Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5)” supports the development of the chemical category inclusive hydrogen cyanide, sodium and potassium cyanides. Hydrogen cyanide (Index No.006-006-00-X) and salts of hydrogen cyanides (Index No.006-007-00-5) are both listed in Annex VI, Table 3.1 of Regulation (EC) No. 1272/2008, entry 006-007-00-5, and are restricted in comparable ways taking into account physical characteristics. Thus, the assignment of ethanedinitrile to a chemical category does not result in a less protective regulatory status.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

Principles of method if other than guideline:
Section 83-3 of the Environmental Protection Agency Guidelines, Subdivision F. for Hazard Evaluation-Ruman and Domestic Animals, issued June, 1982.This is similar to OECD guideline for the testing of chemicals no. 414 for prenatal developmental toxicity study
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
2-hydroxy-2-methylpropionitrile
EC Number:
200-909-4
EC Name:
2-hydroxy-2-methylpropionitrile
Cas Number:
75-86-5
Molecular formula:
C4H7NO
IUPAC Name:
2-hydroxy-2-methylpropanenitrile
Details on test material:
IUCLID4 Test substance: as prescribed by 1.1 - 1.4

Test animals

Species:
rat
Strain:
other: Charles River COBS CD
Details on test animals or test system and environmental conditions:
Source:Charles River Breeding, Labor-atorias. Inc., Portage. Michigan on May 16, 1983

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionised water
Analytical verification of doses or concentrations:
not specified
Frequency of treatment:
daily (gd 6 through 15)
Duration of test:
21 days
Control animals:
yes, concurrent vehicle
Details on study design:
Sex: female

Examinations

Statistics:
no data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Dose selection was made on the basis of marked maternal toxicity observed at higher doses in a range-finding study.
Maternal toxicity was evident by slight reductions in body-weight gain in mid and high exposure groups.

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
1 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
10 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

 


 

Applicant's summary and conclusion

Conclusions:
Acetone cyanohydrin, at oral concentrations 0, 1, 3 or 10 mg/kgbw (corresponding to 0, 0.31, 0.92 and 3.06 mg CNˉ/kgbw), was orally administered to pregnant Sprague-Dawley rats (25/group) on days 6 to 15 of gestation. Concentrations up to 10 mg ACH/kgbw were not teratogenic in the rat, even in the presence of maternal toxicity.
Hydrogen cyanide (Index No.006-006-00-X) and salts of hydrogen cyanides (Index No.006-007-00-5) are both listed in Annex VI, Table 3.1 of Regulation (EC) No. 1272/2008, entry 006-007-00-5, and are restricted in comparable ways taking into account physical characteristics. Thus, the assignment of ethanedinitrile to a chemical category does not result in a less protective regulatory status.