2,6-difluorobenzonitrile

Endpoint summary

Description of key information

ORAL
LD50 = 727.7 mg/kg bw (male rat); sound scientific principles; van Eldik, 1975
INHALATION
LD50 = > 2.64 g/m3 (4h)  male/female rat; OECD 403; Jackosn et al., 1991
DERMAL
LD50 = > 2000 mg/kg bw, male/female rat; EU Method B.3,; Koopman TSM, Busé-Pot TE, 1992

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

727.7 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Value:

mg/kg bw

Additional information

Oral:

The acute oral toxicity of the test material was investigated by administering a single dose of test material by gavage to groups of 5 mice and rats, of each sex, at dose levels of 2.15 µL/kg to 2150 µL/kg body weight (mice) and 100 µL/kg to 2150 µL/kg body weight (rat). All dose levels were brought to a volume of 10 ml/kg of bodyweight with 1% aqueous gum tragacanth. Following dose administration all animals were observed for a period of 14 days and any sign of intoxication ascertained by observation and manipulation was recorded.

Under the conditions of the study, the highest fixed dose of the test material administered without causing any lethality was 578 mg/kg in the mice experiment and 267.9 mg/kg in the rat experiment. The LD50 values were determined to be > 300 < 2000 in all cases.

Supporting information is available in the form of letter submitting study results from an investigation in which male and female rats (5/sex) were given a single oral dose of 0.5 ml/kg. The animals were observed for 15 days. Under the conditions of the study, the median lethal dose of the test material when administered orally to male and female rats was estimated to be greater than 623 mg/kg bw.

The key study is a non-GLP study performed in accordance with generally accepted scientific principles with a sufficient level of detail to assess the quality of the submitted data and was assigned a reliability score of 2; the submitted letter documents a non-GLP study which was not conducted to standard guidelines with incomplete reporting containing an inadequate level of detail to assess the quality of the presented results and was thereby assigned a reliability score of 4.

Inhalation:

The acute inhalation toxicity of the test material was assessed by exposing 3 groups of 5 male and 5 female rats, for a period of 4 hours, to test atmospheres containing the vapour of the test material. Exposure concentrations of 0.19, 0.83 and 2.64 g/m³ were investigated and compared to a control group who were exposed to air only. During the exposure period the animals were continuously observed for any sign of reaction to the test material. Following exposure, the animals were observed at least twice daily during the 14 day observation period. At the end of the observation period the animals were killed and subjected to microscopic and macroscopic examination. During the study none of the animals died. Both the macroscopic results and the microscopic results showed no variations from normal which could be attributed to exposure of the animal to the test material. No changes were seen that were considered to be of any toxicological significance. The acute inhalation median lethal concentration of the test material was estimated to be in excess of 2.64 mg/m³ to both male and female rats.

The study was performed in line with GLP, according to generally accepted scientific principles, and with sufficient detail to assess the quality of the submitted data. It was thereby assigned a reliability score of 1.

 

Dermal:

Five male and five female rats received a single dermal application of 2000 mg/kg of the test material. Animals were assessed over a 14 day observation period for any signs of systemic toxicity. None of the animals died during the study and the clinical signs noted were mostly indicative of effects on motor coordination (abnormal gait and posture). In addition, signs indicative of effects on the autonomic nervous system were observed in one male and female and on the central nervous system in one female only. Time of onset of signs was between 5 and 25 hours after application. Signs were slight to moderate in intensity and had disappeared after 29 hours in males and 3 days in females. After dermal application of the test material the animals showed a decrease in body weights in the first few days of the study. Thereafter body weight gains appeared to be normal. There were no macroscopic abnormalities at examination post-mortem. The acute median lethal dose of the test material was estimated to be in excess of 2000 mg/kg in both male and female rats.

The study was performed in line with GLP, according to standard guidelines, and with sufficient detail to assess the quality of the submitted data. It was thereby assigned a reliability score of 1.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation No. 1272/2008, the test material meets the criteria for classification as 'Acute toxicity oral: Category 4' with the associated hazard phrase 'Harmful if swallowed (H302)'. This is equivalent to Xn (Harmful) with the associated risk phrase 'Harmful if swallowed (R22)' under Directive 67/548/EEC.

In accordance with the criteria for classification as defined in Annex I, Regulation No. 1272/2008, the test material does not require classification for acute inhalation or acute dermal toxicity as no signs of toxicity were noted during the course of the studies.