[(2-chlorophenyl)methylene]malononitrile

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Version / remarks:

not specified, ntp study

Principles of method if other than guideline:

Preliminary study before 2 years study by NTP (1990)

GLP compliance:

not specified

Remarks:

NTP study

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[(2-chlorophenyl)methylene]malononitrile

EC Number:

220-278-9

EC Name:

[(2-chlorophenyl)methylene]malononitrile

Cas Number:

2698-41-1

Molecular formula:

C10H5ClN2

IUPAC Name:

[(2-chlorophenyl)methylene]malononitrile

impurity 1

Reference substance name:

unknown impurities

Cas Number:

Not applicable

Molecular formula:

Not applicable

IUPAC Name:

unknown impurities

Specific details on test material used for the study:

CS2 is 94% o-chlorobenzalmalononitrile (CAS No. 2698-41-1) formulated in a mixture of 5% Cab-0-Sil@ colloidal silica and 1% hexamethyldisilizane (CAS No. 999-97-3). No more details are specified.
No impurities were detected by either thin-layer chromatographic system. Gas chromatographic system 1indicated three unresolved impurities after the major peak, with combined areas of 0.09%relative to the major peak area. Gas chromatographic system 2 indicated two impurities, one before and one after the major peak, with a combined relative area of 0.08%.

Test animals

Species:

other: mise and rats

Strain:

other: Male and female F344/N rats and B6C3F1 mice

Details on species / strain selection:

obtained from the Frederick Cancer Research Facility.

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

other:

Results and discussion

Effect levels

1

Key result

Dose descriptor:

NOAEC

Effect level:

>= 0.075 - <= 0.75 mg/m³ air (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

2

Key result

Dose descriptor:

LOEC

Effect level:

ca. 3 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

mortality

Target system / organ toxicity

Key result

Critical effects observed:

no

Lowest effective dose / conc.:

3 mg/m³ air

System:

respiratory system: upper respiratory tract

Organ:

not specified

Applicant's summary and conclusion

Conclusions:

Thirteen-Week Studies by NTP (1990): because of decreased body weight gain and deaths observed at higher concentrations, exposure concentrations selected for rats for the 2-year studies were 0.075, 0.25, and 0.75 mg/m3, 6 hours per day, 5 days per week. Even though the exposure at highest concentration selected (0.75 mg/m31 resulted in na- sal lesions, their severity was minimal and they were not considered to be life threatening.

Executive summary:

Thirteen-Week Studies by NTP (1990): At exposure concentrations of 0, 0.4, 0.75, 1.5, 3, or 6 mg/m3, 1/10 male rats exposed to 6 mg/m3 died before the end of the studies. Final mean body weights of rats exposed to 1.5 mg/m3 or more were 17%-44% lower than that of controls for males and 10%-24% lower for females. The absolute and relative thymus weights were reduced for exposed male and female rats, particularly at 6 mg/m3. Compound-related lesions of the nasal passage in rats included focal erosion with regenerative hyperplasia and squamous metaplasia of the respiratory epithelium and suppurative inflammation. Acute inflammation and hyperplasia of the respiratory epithelium were seen in the larynx and trachea of some exposed rats.

All mice exposed to 6 mg/m3 and 1/10 males and 1/10 females exposed to 3 mg/m3 died before the end of the studies, Final mean body weights of mice exposed to 3 mg/m3 were 13% lower than that of controls for males and 9% lower for females. Compound-related lesions of the nasal passage in mice included squamous metaplasia of the nasal respiratory epithelium and inflammation.