Reaction mass of 6-butyl-3,6-dihydro-2,4-dimethyl-2H-pyran and 2-butyl-3,6-dihydro-4,6-dimethyl-2H-pyran and 2-butyltetrahydro-6-methyl-4-methylene-2H-pyran

Endpoint summary

Description of key information

Acute Oral Key study : Test for oral toxicity in rats is a key study from O.M. MB Research Laboratories dated on 1980. This acute oral toxicity with male Wistar rats was performed according to an equivalent to OECD 401 guideline.

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:

weight of evidence

Study period:

16 June - 30 June, 1980

Reliability:

4 (not assignable)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Remarks:

This study was conducted in compliance with the FDA's Good Laboratory Practices effective 6/20/79.

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Material Identification (as stated in the report) : Gyrane #80-38
Appearance: Clear liquid
Sample received on 06/02/80

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: 202 - 268 g
- Fasting period before study: 16-20 hours
- Housing: Five animals per cage were housed in suspended wire mesh cages.
- Diet: Fresh Purina rat chow was freely available
- Water: Water was freely available

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test arzicle was given by orally by syringue and a dosing needle.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: the animals were observed 3-4 hours after dosing and once daily for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, toxicity and clinical signs, gross pathology.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

One instance of chromodacryorrhea was noted 3-4 hours post dose.
Isolated instances of hyperactivity, prostration, piloerection, ptosis, tachypnea and chromodacryorrhea were noted during the study. Nine animals were normal on day 14.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity with male Wistar rats performed equivalent to OECD 401 guideline, a LD50 >5000 mg/kg bw was determined.

Executive summary:

Gyrane was tested in an acute oral toxicity study with male Wistar rats at 5000 mg/kg body weight. The study was performed equivalent to OECD 401 guideline and according to GLP principles.

No mortality occurred in 10 male rats from an oral dose of Gyrane, at 5.0 g/Kg. Minimal toxic signs were present and the necropsy findings were normal.

Thus, the LD50 of Gyrane was determined to be : LD50>5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The quality of the key study with a Klimisch score of 4 but with no deaths observed at 5000 mg/kg out of 10 animals, is sufficient for classification determination.

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

Acute Inhalation Toxicity

In line with Column 2, point 8.5.2, Annex VIII of Regulation 1907/2006, an acute inhalation study does not need to be performed as the substance has a low vapour pressure and the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. The acute toxicity endpoint has been addressed by assessing the toxicity via the oral , which is more appropriate when considering the properties of this substance.

Acute Dermal Toxicity

An acute dermal toxicity study does not need to be performed as the substance doe snot meet the criteria for classification as acute toxicity or STOT SE by the oral route (LD50 oral > 5000 mg/kg bw) and no systemic effects have been observed in the in vivo studies with Dermal exposure ( skin irritation and sensitization studies).

Justification for classification or non-classification

In the key study, no mortality occurred in 10 male rats from an oral dose of Gyrane, at 5.0 g/Kg. Minimal toxic signs were present and the necropsy findings were normal. Thus, the LD50 of Gyrane was determined to be : LD50>5000 mg/kg bw. Therefore, in accordance with Regulation (EC) No. 1272/2008, the substance does not meet the GHS criteria for classification for acute oral toxicity.