5H-Cyclopenta[h]quinazoline, 6,7,8,9-tetrahydro-7,7,8,9,9-pentamethyl-

Endpoint summary

Description of key information

- Acute oral toxicity: LD50 is 500 mg/kg bw in an OECD TG 423

- Acute inhalation toxicity: LC50 is >5.02 mg/L in an OECD TG 403

- Acute dermal toxicity: LD50 is >2000 mg/kg bw in an OECD TG 402

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 5.02 mg/L air

Physical form:

inhalation: dust / mist

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute toxicity oral (OECD 423):

The study was performed according to OECD TG 423, conducted in compliance with GLP, to assess the acute oral toxicity of the substance in the Wistar strain rat. A group of three fasted females was treated with the substance at a dose level of 300 mg/kg body weight. Based on the results from this dose level, further groups of fasted females were treated at dose levels of 300 and 2000 mg/kg body weight. Dosing was performed sequentially. The substance was administered orally as a suspension in arachis oil BP. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

The animals treated at a dose level of 2000 mg/kg were killed for humane reasons, four hours after dosing, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence. There were no deaths at a dose level of 300 mg/kg. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were hunched posture, ataxia, lethargy, body tremors, or occasional body tremors, hypothermia, decreased respiratory rate, clonic and tonic convulsions, splayed gait and ptosis. There were no signs of systemic toxicity at a dose level of 300 mg/kg. Surviving animals showed expected gains in body weight. White liquid present in the stomach was noted in animals treated at a dose level of 2000 mg/kg. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.

In conclusion, the acute oral median lethal dose (LD50) of the substance in the female Wistar strain rat was approximately 500 mg/kg body weight.

Acute toxicity inhalation (OECD 403):

A study was performed to assess the acute inhalation toxicity of the substance according to OECD TG 403. A group of 10 RccHan™: WIST strain rats (5 males and 5 females) was exposed to a dust atmosphere. The animals were exposed for 4 hours using a nose only exposure system, followed by a 14 day observation period.

The particulate concentration achieved was measured gravimetrically and found to be 5.02 mg/L The test atmosphere had a mass median aerodynamic diameter of 7.04 µm and a geometric standard deviation (GSD) of 2.59; the inhalable content (%<4 µm) was 27.5%.

Common abnormalities noted during the study included increased respiratory rate, hunched posture, pile-erection and wet fur. There were frequent instances of tip-toe gait and occasional instances of ataxia and red/brown staining around the snout. Isolated occurrences of decreased respiratory rate, laboured respiration, dehydration, diuresis, dehydration, ptosis and occasional body tremors were also noted. The surviving animals recovered to appear normal from days 6 to 11 post-exposure. All animals exhibited body weight losses on the first day post-exposure. All male animals exhibited body weight gains during the remainder of the recovery period. In contrast, all surviving female animals exhibited further body weight losses or showed no body weight gains from days 1 to 3 post-exposure. The surviving animals then exhibited body weight gains during the remainder of the recovery period. With the exception of one instance of dark patches on the lungs, no macroscopic abnormalities were detected at necropsy amongst animals that survived until the end of the fourteen day recovery period.

Based on these results, the LC50 is determined to be greater than 5.02 mg/L.

Acute toxicity dermal (OECD 402):

The study was performed to assess the acute dermal toxicity of the substance in the Wistar strain rat. Initially, two animals (one male and one female) were given a single, 24 hour, semi occluded dermal application of the substance to intact skin at a dose level of 2000 mg/kg body weight. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results showed that there were no deaths. There were no signs of systemic toxicity. Very slight erythema was noted at the test sites of three females. Small superficial scattered scabs and scab lifting to reveal glossy skin were also noted at the test site of one female. There were no signs of dermal irritation noted at the test sites of the remaining animals. All animals showed expected gains in body weight. No abnormalities were noted at necropsy.

In conclusion, the acute dermal median lethal dose (LD50) of the substance in the Wistar strain rat was found to be greater than 2000 mg/kg body weight. The substance does not meet the criteria for classification according to the Globally Harmonized System of Classification and Labeling of Chemicals and Regulation (EC) No 1272/2008, relating to the Classification, Labeling and Packaging of Substances and Mixtures.

Justification for classification or non-classification

The substance needs to be classified for acute oral toxicity, category 4, based on an LD50 of 500 mg/kg bw and labelled with H302: Harmful if swallowed according to EU CLP Regulation (EC No. 1272/2008 and its amendments).

The substance does not need to be classified for acute inhalation toxicity based on LC50 >5020 mg/m3 according to EU CLP (EC 1278/2008 and its amendments).

The substance does not need to be classified for acute dermal toxicity based on an LD50 >2000 mg/kg bw according to EU CLP (EC 1278/2008 and its amendments).