Reaction mass of (1S*, 2R*, 5S*)-2-Isopropenyl-5-methylcyclohexanol and (1S*, 2S*, 5R*)-2-Isopropenyl-5-methylcyclohexanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 Nov - 12 Dec 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 Dec 2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (1S*, 2R*, 5S*)-2-Isopropenyl-5-methylcyclohexanol and (1S*, 2S*, 5R*)-2-Isopropenyl-5-methylcyclohexanol

Molecular formula:

C10H18O

IUPAC Name:

Reaction mass of (1S*, 2R*, 5S*)-2-Isopropenyl-5-methylcyclohexanol and (1S*, 2S*, 5R*)-2-Isopropenyl-5-methylcyclohexanol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 180.2 - 219.3 g
- Fasting period before study: Animals were fasted overnight approx. 16 h prior to dosing and 4 h post dosing.
- Housing: individually in stainless wire mesh cages (260W×350D×210H mm)
- Diet: Pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C), ad libitum
- Water: public tap water filtered and irradiated by UV-light, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 - 24.6
- Humidity (%): 47.0 - 61.7
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 400 and 60 mg/mL
- Amount of vehicle: 5 mL/kg bw
- Lot/batch no.: MKBV2080V, MKBW9504V

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: Due to the low expected toxicity of the test substance, 2,000 mg/kg was selected as the starting dose for this study based on the information supplied by the sponsor.

Doses:

2000 mg/kg bw (step 1 and 2), 300 mg/kg bw (step 3 and 4)

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min and 1, 2, 4 and 6 h after dosing and thereafter once daily for 14 days. Individual body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy, Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Mean scores and values were determined.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg bw: 0/3 animals (step 1) and 2/3 animals (step 2) at Day 4
300 mg/kg bw: 0/3 animals (step 3) and 0/3 animals (step 4)

Clinical signs:

2000 mg/kg bw: In surviving animals abnormal gait was observed in four animals at 0.5 - 6 h after dosing, and a decrease of fecal volume was observed in four animals on Day 1, fully reversible 48 h. In dead animals abnormal gait was observed in two animals at 0.5 - 4 h after dosing, and lacrimation, loss of locomotor activity and lying on side were observed in two animals at 6 h after dosing to Day 3 and additional signs as no stool and refusal to feed from Day 1 to Day 3. Then, these animals were found dead in a state of lying on side on Day 4.
300 mg/kg bw: No abnormalities of clinical signs were observed in any animal throughout the study.

Body weight:

2000 mg/kg bw: In surviving animals a tendency for suppression of body weight gain was observed in one animal on Day 1. Then, normal body weight gain was observed in these animals on Day 3. In dead animals, a decrease in body weight was observed in two animals on Day 1 and Day 3.
300 mg/kg bw: Body weight gains were within the normal ranges during the whole study period.

Gross pathology:

No grossly visible findings were observed in any animal at 300 and 2000 mg/kg.

Any other information on results incl. tables

Table 1. Results of the acute oral toxicity study.

Dose level (mg/kg bw)	Mortalities	Clinical signs
	n
2000 (step 1)	0/3	3/3
2000 (step 2)	2/3	3/3
300 (step 3)	0/3	0/3
300 (step 4)	0/3	0/3

Applicant's summary and conclusion

Interpretation of results:

other: Acute Tox. Cat. 4 according to Regulation (EC) No 1272/2008

Conclusions:

In this acute oral toxicity study in female rats a LD50 cut-off value of 2000 mg/kg bw was found.

Executive summary:

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 423 and in compliance with GLP (2017). In step 1, the test substance was administered via oral gavage to 3 female rats at dose level of 2000 mg/kg bw. Since no mortality occurred, 2000 mg/kg bw was administered to 3 further animals in a second step. Two animals were found dead on Day 4 after administration. Therefore, 300 mg/kg bw was administered to 3 animals each in step 3 and 4. No mortality was observed at 300 mg/kg bw. Based on the results a LD50 cut-off of 2000 mg/kg bw was determined in this study.