Cyclohexanone, 2-methyl-4-(1,1,2-trimethylpropyl)-, cis-

Endpoint summary

Description of key information

The acute oral toxicity in rats: LD50 >2,000 mg/kg and LD50 cut-off cvalue >5,000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted by GLP accredited laboratory. Method according to OECD guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Six female Sprague-Dawley rats (SPF Caw) from Elevage JANVIER, France of 8 weeks old were selected having body weights from 181-199g.
A controlled environment was maintained in the room with optimal conditions of approximately 15/h air changes, a temperature of 19-25ºC, a relative humidity of 30-70% and a 12 hour light/12 hour dark cycle per day (light cycle 7.00-19.00h).
3 animals were present in a solid-bottomed polycarbonate cage with a stainless steel mesh lid containing sawdust bedding that was exchanged twice a day. Animals were acclimitised for a period of 5 days prior to exposure. The animals had free access to tap water and food (M20, SDS).

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test item was administered by gavage under a volume of 2.19 mL/kg body weight (corresponding to 2 g/kg, according to the calculated density) using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

The dose level was 2000 mg/kg (2.19 ml/kg body weight) on day 0.

No. of animals per sex per dose:

3 female rates per group. Two groups of rats.

Control animals:

yes

Details on study design:

The animals were daily systematically examined on behavioural or toxic effects on the major physiological functions at 0.5, 1, 3, 4 and 24 hours after the administration of the test item and daily during 14 days following the administration of the test item. Symptoms were recorded as "present" or "absent" on the observation sheet. These observations were compared to historical control data. The animals were observed for the presence of spontaneous activity, preyer’s reflex (noise), respiratory rate, convulsions, tremors, body temperature, muscle tone, palpebral opening, pupil appearance, salivation, lachrymation, righting reflex and back hair appearance.
Animals were weighed on days 0 (just before administration), 2, 7 and 14.
On day 14, the animals were anaesthetised with sodium pentobarbital. Macroscopic observations were entered on individual autopsy sheets. Only those organs that were likely to be modified in case of acute toxicity were examined.

Statistics:

The method used is not intended to calculate a precise LD50, hence no statistical analysis was performed. The oral LD50 was ranked and an LD50 cut-off value determined based on the OECD 423 guideline.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: cut-off value

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs related to the administration of the test item were observed during the study.

Gross pathology:

The macroscopical examination of the animals at the end of the study did not reveal treatment related changes.

Table 1 Body weight and weight gain in grams of the six female rats subjected to the test substance at a dose of 2,000mg/kg bw.

	D0	D2	D2-D0	D7	D7-D0	D14	D14-D0
Females
Rf 0181	187	204	17	217	30	229	42
Rf 0182	186	193	7	210	24	227	41
Rf 0183	181	191	10	206	25	221	40
Rf 0192	198	206	8	226	28	242	44
Rf 0193	194	205	11	213	19	240	46
Rf 0194	191	202	3	222	23	234	35
Mean	190.8	202.2	9.3	215.7	24.8	232.2	41.3
Std Dev	7.3	6.5	4.7	7.5	3.9	8.0	3.8

Dx (x=0,2,7,14) stands for the number of days after the administration of the test substance.

 

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The oral LD50 of the test substance in Wistar rats exceeds 2,000 mg/kg body weight. the LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg body weight by oral route in the rat.

Executive summary:

The acute toxicity class method (OECD 423 (2001)) was used to assess the acute toxicity of test substance in 6 female Sprague-Dawley rats.

The test substance was administered by oral gavage to the rats at a dose level of 2,000 mg/kg body weight. Animals were observed daily and their body weights were weekly recorded. Macroscopic examination was performed after sacrifice.

No mortality occurred and no clinical signs related to the administration of the test item were observed. The body weight gain was normal.

No abnormalities were found at post mortem macroscopical examinations of the animals.

The LD50 of the test substance exceeds 2,000 mg/kg body weight. Based on the result, the LD50 cut-off value may be considered >5,000 mg/kg body weight.

Consequently, the test substance does not need to be classified for acute oral toxicity according to Regulation EC No. 1272/2008 and GHS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of acute toxicity – oral endpoint

Study conducted on substance by a GLP accredited laboratory. Method according to OECD guideline.

Justification for classification or non-classification

The LD50 of the test item IRISWOOD is higher than 2,000 mg/kg body weight by oral route in the rat. In accordance with the OECD guideline No. 423, the LD50 cut-off of the test item may be considered to be higher than 5,000 mg/kg body weight by oral route in the rat. According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the EEC Directives 67/548, 2001/59 and 99/45, the test item IRISWOOD must not be classified. No symbol or risk phrase is required. In accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures, the test item must not be classified. No signal word or hazard statement is required.