Condensation products of oil shale alkylresorcinols and formaldehyde

Endpoint summary

Description of key information

Oral:
The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated as being greater than 2000 mg/kg bodyweight.
Inhalation: In accordance with standard information requirement 8.5 of Annex VIII of Regulation (EC) No. 1907/2006, Column 2 states that an acute toxicity study by either the inhalation or dermal route shall be provided. The choice of study shall be dependent on the nature of the substance and the likely route of exposure. Due to the solid nature and low vapour pressure of the substance (less than 1.2 x 10-3 Pa at 25 ºC), the dermal route is considered a more likely route of exposure than inhalation, therefore the acute toxicity study via the inhalation route is omitted.
Dermal:
The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

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:

30 March 2004 and 21 April 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (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:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK.
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 193 - 209 g
- Fasting period before study: overnight fast immediately before dosing and 3 to 4 hours ater dosing
- Housing: animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): free access to certified rat and mouse feed
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: at least five days
- Other: The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

IN-LIFE DATES: From: 30 March 2004 To: 21 April 2004

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: material does not dissolve in water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg (the volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing)

DOSAGE PREPARATION:
For the purpose of the study the test material was ground to a powder and then freshly prepared, as required, as a suspension at the appropriate concentration in arachis oil BP. Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: material not expected to be toxic

Doses:

single

No. of animals per sex per dose:

6 (two groups of 3 animals)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology.

Statistics:

none

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None of the animals died during the study.

Clinical signs:

other: Signs of systemic toxicity noted during the study were hunched posture, increased salivation, pilo-erection, noisy respiration and red/brown staining around the mouth. Animals appeared normal one or two days after dosing.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated as being greater than 2000 mg/kg bodyweight.

Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The study used 6 female rats and followed the actute toxic-class method, in accordance with the OECD 423 guideline. The study was conducted to GLP standard in a certified laboratory.

All clinical signs observed had disappeared within 2 days. Bodyweight gain remained normal and no abnormalities were revealed at necrospy. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The one study available is considered to have a reliability score of 1 in accordance with the scoring system of Klimisch et. al. (1997). The quality of the database is high.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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

Study period:

31 March 2004 and 14 April 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK.
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: At least 200g. The weight variation did not exceed ± 20% of the mean weight for each sex.
- Housing: Solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): free access to certified rat and mouse diet
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: at least five days
- Other: The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%):30 to 70 %
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

IN-LIFE DATES: From: 31 March 2004 To: 14 April 2004.

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: On the day before treatment the back and flanks of each animal were clipped free of hair. Test material was spread evenly over the area.
- % coverage: 10 % of body surface
- Type of wrap if used: a piece surgical gauze placed over the treatment area and semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): test material was moistened with arachis oil BP

Duration of exposure:

24 h

Doses:

1

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, skin reactions (examined daily according to Draize (1977) method.

Statistics:

none

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None of the animals died during the study.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

Effects on organs: No abnormalities were noted at necropsy.

Other findings:

Local effects: Very slight to well-defined erythema was noted at all treatment sites in both male and female rats. All signs had disappeared by the fourth day.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. Five male and five female rats were given a single dermal application of the test material at 2000 mg/kg bodyweight. The test was conducted in accordance with the OECD 402 and EU Method B.3 guidelines. The study was performed to GLP standard in a certified laboratory.

Under the conditions of the study the acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The one study available is considered to have a reliability score of 1 in accordance with the scoring system of Klimisch et. al. (1997). The quality of the database is high.

Additional information

ORAL

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The study used 6 female rats and followed the acute toxic-class method, in accordance with the OECD 423 guideline. The study was conducted to GLP standard in a certified laboratory.

All clinical signs observed had disappeared within 2 days. Bodyweight gain remained normal and no abnormalities were revealed at necropsy. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated as being greater than 2000 mg/kg bodyweight.

DERMAL

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. Five male and five female rats were given a single dermal application of the test material at 2000 mg/kg bodyweight. The test was conducted in accordance with the OECD 402 and EU Method B.3 guidelines. The study was performed to GLP standard in a certified laboratory.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Justification for selection of acute toxicity – oral endpoint
Only one study was available to address this endpoint. The study was considered to be reliable enough to address this endpoint alone, and is therefore is selected as the key study.

Justification for selection of acute toxicity – inhalation endpoint
The study was omitted as the dermal route was considered more appropriate.

Justification for selection of acute toxicity – dermal endpoint
Only one study was available to address this endpoint. The study was considered to be reliable enough to address this endpoint alone, and is therefore is selected as the key study.

Justification for classification or non-classification

In accordance with criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification as no signs of toxicity were noted during the course of the acute oral, or acute dermal, toxicity studies.