Oxalonitrile

Toxicity to reproduction

Administrative data

Endpoint:

reproductive toxicity, other

Remarks:

A 90-Day Oral (Drinking Water) Toxicity Study of Soduium Cyanide in Male Fisher F344/DuCrl Rats with a 70-Day Recovery Period

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD408

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Sodium cyanide

EC Number:

205-599-4

EC Name:

Sodium cyanide

Cas Number:

143-33-9

Molecular formula:

CNNa

IUPAC Name:

sodium cyanide

Test animals

Species:

rat

Strain:

Fischer 344/DuCrj

Sex:

male

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Remarks:

reverse osmosis water

Details on exposure:

Drinking water offered continuously for a minimum of 91 consecutive days.

Duration of treatment / exposure:

minimum 91 days

Frequency of treatment:

continuously

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

3 ppm

Doses / concentrations 2

Dose / conc.:

10 ppm

Doses / concentrations 3

Dose / conc.:

30 ppm

Doses / concentrations 4

Dose / conc.:

100 ppm

Doses / concentrations 5

Dose / conc.:

300 ppm

No. of animals per sex per dose:

10 main study
10 recovery study

Control animals:

yes

other:

Examinations

Sperm parameters (parental animals):

Motility
Cauda epididimis, LT WT
Cauda epididimis KT CONC
Sperm morphology
Testis, LT WT
Testis LT CONC
Sperm production rate
Seminal vesicle, Prostate

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Reproductive function / performance (P0)

Reproductive function: sperm measures:

no effects observed

Effect levels (P0)

1

Key result

Dose descriptor:

NOEL

Effect level:

100 ppm

Based on:

test mat.

Sex:

male

Basis for effect level:

organ weights and organ / body weight ratios

2

Key result

Dose descriptor:

NOAEL

Effect level:

300 ppm

Based on:

test mat.

Sex:

male

Basis for effect level:

organ weights and organ / body weight ratios

Target system / organ toxicity (P0)

Key result

Critical effects observed:

no

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Effect levels (F1)

Remarks on result:

not measured/tested

Overall reproductive toxicity

Key result

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

There were no statistically significant differences when the ad libitum control group (Group 1)
was compared to the restricted water control group (Group 2) and the test substance-treated
groups, or when the restricted water control group was compared to the 300 ppm group. While
mean values for sperm motility, cauda epididymides and testes weights, and sperm production
rate in the 300 ppm group were slightly lower compared to the ad libitum control group (Group
1), most individual values remained within the range of values observed in the ad libitum control
group (Group 1) and therefore this was attributed to biological variation and was not considered
test substance-related.