4-(3-methylbut-2-en-1-yl)phenol

Endpoint summary

Description of key information

The key oral LD50 value (>300 mg/kg and <2000 mg/kg) is derived from a gavage study in Sprague-Dawley rats according to OECD test guideline 420. At 300 mg/kg, no abnormalities in gross pathology, nor any clinical symptoms were detected. Gross pathology at 2000 mg/kg showed lungs abnormally red, dark liver, dark kidneys, haemorrhagic and ulcerated gastric mucosa and a haemorrhagic non-glandular epithelium of the stomach.
Clinical signs of toxicity showed hunched posture, lethargy, ataxia, decreased respiratory rate, loss of righting reflex, laboured respiration, ptosis, hypothermia, urine stained red and finally killed in extremis at 2000 mg/kg. 

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

Study period:

2008-09-30 to 2008-10-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD test guideline 420

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, United Kingdom
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 156 - 187 g
- Fasting period before study: overnight before dosing
- Housing: polypropylene cages with woodflakes
- Diet (e.g. ad libitum): 2014 Teklad Global Rodent diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 7
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL (300 mg/kg). For 2000 mg/kg, the test material was used as supplied (undiluted)
- Amount of vehicle (if gavage): 10 mL (300 mg/kg), 2.04 mL (2000 mg/kg)
- Justification for choice of vehicle: test substance not soluble in water

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: absence of toxicity data

Doses:

300, 2000 mg/kg

No. of animals per sex per dose:

300 mg/kg: 5
2000 mg/kg: 1

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observtions made 0.5, 1, 2 and 4 hours after dosing then daily up to day 14. Body weights were recorded on day 0, 7 and 14 after dosing (or at day of death)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
- Other: Following the sighting test at dose levels of 2000 mg/kg (one animal) and 300 mg/kg (one animal), a further group of four fasted female rats was given a single oral dose of 300 mg/kg test material due to mortality and signs of systemic toxicity at the dose level of 2000 mg/kg.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg: 1/1
300 mg/kg: 0/5

Clinical signs:

2000 mg/kg: hunched posture, lethargy, ataxia, decreased respiratory rate, loss of righting reflex, laboured respiration, ptosis, hypothermia, urine stained red, killed in extremis
300 mg/kg: no signs of systemic toxicity

Body weight:

2000 mg/kg: 170 g
300 mg/kg: 179 - 216 g

Gross pathology:

2000 mg/kg: lungs abnormally red, dark liver, dark kidneys, haemorrhagic and ulcerated gastric mucosa, haemorrhagic non-glandular epithelium of the stomach
300 mg/kg: no abnormalities detected

Individual bodyweights and bodyweight changes

Dose level  [mg/kg]	Animal number and sex	Bodyweight [g] at day			Bodyweight [g] at death	Bodyweight gain [g] during week
		0	7	14		1	2
2000	2-0 female	176	-	-	170	-	-
300	1-0 female	156	166	179	-	10	13
300	3-0 female	184	192	216	-	8	24
300	3-1 female	187	197	203	-	10	6
300	3-2 female	179	181	200	-	2	19
300	3-3 female	187	199	200	-	12	1

Individual clinical obervations and mortality data

Dose level  [mg/kg]	Animal number and sex	Effects noted after dosing [h]				Effects noted during period after dosing [d]
		0.5	1	2	4	1 – 14
2000	2-0 female	H L A Rd	H L A Rd	Rd Rl Rr Pt Ho U X	-	-
300	1-0 female	0	0	0	0	0
300	3-0 female	0	0	0	0	0
300	3-1 female	0	0	0	0	0
300	3-2 female	0	0	0	0	0
300	3-3 female	0	0	0	0	0

H: hunched posture; L: lethargy; A: ataxia; Rd: decreased respiration rate; Rl: laboured respiration; Rr: loss of righting reflex; Pt: ptosis; Ho: hypothermia; U: urine stained red; X: animal killed in extremis

Necropsy findings

Dose level  [mg/kg]	Animal number and sex	Time of death [d]	Macroscopic observations
2000	2-0 female	0 in extremis	Lungs: abnormally red; liver: dark; kidneys: dark; gastric muscosa: haemorrhagic, ulcerated; non-glandular epithelium of the stomach: hamorrhagic
300	1-0 female	14 (killed)	No abnormalities detected
300	3-0 female	14 (killed)	No abnormalities detected
300	3-1 female	14 (killed)	No abnormalities detected
300	3-2 female	14 (killed)	No abnormalities detected
300	3-3 female	14 (killed)	No abnormalities detected

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 was determined to be >300 and <2000 mg/kg. Therefore, the substance should be classified as harmful if swallowed according to Regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

For the oral route, there is one Klimisch 1 study, so it was selected as the key study. The LD50 value was determined to be >300 and <2000 mg/kg.

Justification for selection of acute toxicity – oral endpoint
GLP study according to OECD test guideline 420

Justification for classification or non-classification

This substance is to be labeled as 'H302 Harmful if swallowed', the proposed hazard class under Regulation 1272/2008 is 'Acute Tox. 4 (oral)' based on an acute oral LD50 of >300 mg/kg and <2000 mg/kg.