Guaiacol

Endpoint summary

Description of key information

LD50 oral on rat: 621-725 mg/kg (published data)(reliability 2)
LC50 inhalation on mice (2h): 7.57 mg/L (published data)(reliability 4)  
LD50 dermal on rabbit: 4600 mg/kg (published data)(reliability 2)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The purity of the test substance was unknown. A range of doses was only precised: the number of doses were unknown. The GLP were not mentioned but the study was performed before the GLP standard was established.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

not specified

Test type:

other: acute oral toxicity

Species:

rat

Strain:

other: Osborne-Mendel or Sherman

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Age at study initiation: young adult
No more data

ENVIRONMENTAL CONDITIONS: no data
In-life dates: no data

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

not detailed

No. of animals per sex per dose:

5 males and 5 females at each dose.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: until the survivors had return to normal in appearance and weight
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs

Statistics:

Litchfield and Wilcoxon method.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

725 mg/kg bw

95% CL:

302 - 1 740

Mortality:

Death occurred from 1 hour to 4 days after the gavage

Clinical signs:

other: Marked depression and comatose were noted at higher doses.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on this study, the substance is classified: Acute Tox. Category 4, H302 according to EU GHS criteria.

Executive summary:

In an acute oral toxicity study (Taylor, 1964), groups of young adults male/female Osborne-Mendel or Sherman rats were given a single oral dose of  guaiacol (doses unspecified), and were observed until survivors had return to normal in appearance and weight.
 
Oral LD50 Combined = 725 mg/kg  bw (with 302-1740 95% C.I.).

Guaiacol is harmful by ingestion (classified acute. Tox. Cat.4, H302) based on the LD50 of 725 mg/kg bw/day identified in both sex and according to the EU classification criteria (Annex VI of Directive 67/548/EEC and Annex I of Regulation (EC) n°1272/2208).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The purity of the test substance was unknown. The number of doses was unknown and the GLP were not mentioned. The results were described in details.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

not specified

Test type:

standard acute method

Species:

mouse

Strain:

Swiss

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: male/female
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 20-25 g
- Fasting period before study: no data
- Housing: no data
- Food consumption: ad libitum
- Water consumption: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data
In-life dates: no data

Route of administration:

oral: gavage

Vehicle:

other: 0.5% methylcellulose solution

Details on oral exposure:

* Vehicle:
- Concentration in vehicle: 0.5%
* Maximum dose volume applied: 20 mL/kg bw

Doses:

Not detailed

No. of animals per sex per dose:

56 animals for all test

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs

Statistics:

Litchfield and Wilcoxon

Sex:

male/female

Dose descriptor:

LD50

Effect level:

621 mg/kg bw

95% CL:

565 - 682

Clinical signs:

other: Lacrimation and motor incoordination were observed at low doses (301 mg/kg bw), and tremor and dyspnea were noted at higher doses (421 mg/kg bw).

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on this study the substance is classified: Acute Tox Category 4 according to EU GHS criteria.

Executive summary:

In an acute oral toxicity study (Cioli, 1980), groups of Swiss mice (male/female) were given a single oral dose of  guaiacol at 0.5% in methylcellulose. Doses were not specified, and animals were observed for 14 days.
 
Oral LD50 Combined = 621 mg/kg  bw (with 565-682 95% C.I.).

Guaiacol is harmful by ingestion (classified acute tox. cat. 4, H302) based on the LD50 of 621 mg/kg bw/day identified in both sex and according to the EU classification criteria (Annex VI of the Directive 67/548/EEC and Annex I of the Regulation (EC) n°1272/2008).

This classification is in accordance with the official classification according to Annex VI table 3 of the Regulation (EC) n°1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

621 mg/kg bw

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The purity of the test substance, the vehicle, the strain and the sex of the rabbits were not reported. The protocol appeared to be similar from the standard method. The GLP were not mentioned but the study was performed before the GLP standard was established.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute dermal toxicity

GLP compliance:

no

Test type:

other: dermal toxicity

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

ADMINISTRATION / EXPOSURE: on abraded or intact skin
No more details

Duration of exposure:

no data

Doses:

2500, 3530, 5000 mg/kg bw

No. of animals per sex per dose:

4 animals per dose, sex unspecified.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: no data
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross examination

Statistics:

Harris method

Sex:

not specified

Dose descriptor:

LD50

Effect level:

4 600 mg/kg bw

95% CL:

> 3 800 - < 5 400

Remarks on result:

other: In the same study, dermal irritation was evaluated.

Mortality:

3/4 animals at 5000 mg/kg bw

Clinical signs:

other: at 2500 and 3530 mg/kg bw slight diarrhea was noted. At 5000 mg/kg bw, 3/4 rabbits died on days 1 and 8 and slight diarrhea, anorexia, lethargy, pilorection, emaciation, yellowish discharge at nose, ataxia and flaccid muscle tone were observed.

Gross pathology:

Necropsy revealed no abnormalities in all animals treated with 3530 mg/kg bw and in 2/4 rabbits treated with 2500 mg/kg bw.
At 2500 mg/kg bw dose level, red areas in intestines were observed in 2/4 animals; dark liver in 2/4 animals; large spleen in 1/4 animals; skin
hard/thick in 1/4 animals.
At 5000 mg/kg dose level, necropsy revealed red exudate in the nose/mouth in 2/4 rabbits; brown anogenital exudate in 1/4 animals; red anogenital exudate in 1/4 animals; red areas in intestines in 2/4 animals; bloated intestines in 1/4 animals; stomach covered with blue-white dots in 1/4 animals; dark liver in 1/4 animals; mottled liver in 2/4 animals; dark lungs in 2/4 animals; dark kidney in 1/4 animals; dark spleen in 1/4 animals; skin edema
in 1/4 animals; skin redness in 1/4 animals; and blood in urine in 2/4 animals.

Other findings:

no data

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Based on this test, the substance is not classified according to EU GHS criteria and classified Acute. Tox. Cat. 5, H313 according to GHS UN criteria.

Executive summary:

In an acute dermal toxicity study (Moreno, 1978), groups of 4 rabbits (sex unspecified) were dermally exposed to guaiacol at doses of 2500, 3530 and 5000 mg/kg bw.

Dermal LD50 = 4600 mg/kg bw (95% C.I: 3800-5400 mg/kg).

Guaiacol is not classified based on the LD50 of 4600 mg/kg bw/day identified in this study and according to EU classification criteria (Annex VI of Directive 67/548/EEC and Annex I of Regulation (EC) n°1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 600 mg/kg bw

Additional information

Oral:

Two studies were selected as key studies (available in different publications) and give the following LD50 in rats by oral route: 621 and 725 mg/kg. Studies were well described and the reliability of these two studies is 2 according to Klimisch ranking.

 

Dermal:

Only one study was available and was considered as a key study. The reliability of this study is 2 according to Klimisch ranking. In this acute dermal toxicity study (Moreno, 1978), groups of 4 rabbits (sex unspecified) were dermally exposed to guaiacol at doses of 2500, 3530 and 5000  mg/kg bw. Dermal LD50 was 4600 mg/kg bw (95% C.I:3800-5400mg/kg).

 

Inhalation:

Only one study was available. The reliability of this study is 4 according to Klimisch ranking. In this acute inhalation toxicity study (Ostrovsky, 1964), groups of mice were exposed by inhalation route to guaiacol for 2 hours at concentrations of 2.03 to 17.19mg/L.The LC50 in mice was 7.57 mg/L for 2 hours (calculated as 3.78 mg/L for 4 hours).

 

Justification for classification or non-classification

Oral: Based on the LD50 value of 621 mg/kg bw/day, gaiacol is classified as Acute Tox. Category 4, H302:Harmful if swallowed according to EU GHS criteria (Regulation (EC) n° 1272/2008 - Annex I). This classification is in accordance with the official one.

Dermal: Based on the dermal LD50 of 4600 mg/kg bw/day, gaiacol is not classified for dermal acute toxicity according to EU GHS criteria (Regulation (EC) n°1272/2008 - Annex I). This classification is in accordance with the official one.

 

Inhalation: Based of the LC50 of 7.57 mg/L calculated in mice for 2 hours of exposure (calculated as 3.78 mg/L for 4 hours) no conclusion on guaiacol classification can be drawn for this endpoint, since this study was performed in mice instead of rats and during only 2 hours instead of 4 as required in the OECD guideline.

However, gaiacol was not officially classified for this route of exposure.

 

Gaiacol is officially classified as Acute Tox. Category 4, H302: Harmful if swallowed according to the Regulation (EC) n° 1272/2008 Annex VI table 3.