Petrolatum (petroleum), oxidized, Bu ester

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg bw, female rat, OECD 423, Kuthy (2012)

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:

10 October 2012 to 26 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from the standard test guideline and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

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:

other: Crl:(WI)BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi Coop Zrt., Cserkesz u. 90., 1103 Budapest, Hungary
- Age at study initiation: 8 weeks
- Weight at study initiation: 181 - 195 g (group 1); 196 - 213 (group 2)
- Fasting period before study: animals were fasted overnight the day before treatment. Food was returned 3 hours after treatment.
- Housing: 3 animals were housed in each Type II polypropylene/polycarbonate cage (by group)
- Diet: ssniff® SM R/M-Z+H complete diet for rats and mice (ssniff Spezialdiäten GmbH, D-59494 Soest, Germany) ad libitum
- Water: tap water ad libitum
- Acclimation period: 13 days (group 1); 14 days (group 2)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 8 - 12 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Route of administration:

oral: gavage

Vehicle:

other: Helianthi annui oleum raffinatum

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS
All doses were formulated in the vehicle. Concentration of formulations was adjusted to maintain a treatment volume of 10 mL/kg bw. The test material was applied in a concentration of 200 mg/mL. Formulations were prepared just before administration and stirred continuously during the treatment.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: the starting dose was selected on the basis of the available information on the test material.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: animals were observed for mortality after dosing at least once during the first 30 minutes then 1, 2, 3 and 4 hours after treatment then twice daily thereafter. Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremours, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Frequency of weighing: body weights were recorded on day 0 (just before treatment), on day 7 and on day 15 with a precision of 1 g.
- Necropsy of survivors performed: yes. At the end of the observation period all rats were sacrificed under isofluran anaesthesia. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed, and any abnormality was recorded with details of its location, colour, shape and size.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the study.

Clinical signs:

other: No treatment-related symptoms were observed, throughout the 14-day post-treatment period, in any of the treated animals.

Gross pathology:

Autopsy revealed no pathological changes.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the acute oral LD50 of the test material was determined to be in excess of 2000 mg/kg bw. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.

Executive summary:

The acute oral toxicity of the test material was investigated in a GLP study which was conducted in accordance with the standardised guideline OECD 423, following the acute toxic class method. During the study a group of 3 female rats received a single oral dose of 2000 mg/kg bw test material. Animals were observed for mortality and clinical signs for14 days following treatment. Since no animal died in the first step, treatment with 2000 mg/kg bw was repeated on a further three female rats. As no animals died in the second step, testing was terminated. No treatment-related symptoms were observed, throughout the 14-day post-treatment period, in any of the treated animals and no treatment-related changes in body weight were noted throughout the study. Autopsy revealed no pathological changes. Under the conditions of the study, the acute oral LD50 of the test material was determined to be in excess of 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Study conducted in compliance with agreed protocols, with no or minor deviations from the standard test guideline and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions. The study was therefore assigned a reliability score of 1 according to the criteria of Klimisch (1997).

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

Oral

The acute oral toxicity of the test material was investigated in a GLP study which was conducted in accordance with the standardised guideline OECD 423, following the acute toxic class method. During the study a group of 3 female rats received a single oral dose of 2000 mg/kg bw test material. Animals were observed for mortality and clinical signs for14 days following treatment. Since no animal died in the first step, treatment with 2000 mg/kg bw was repeated on a further three female rats. As no animals died in the second step, testing was terminated. No treatment-related symptoms were observed, throughout the 14-day post-treatment period, in any of the treated animals and no treatment-related changes in body weight were noted throughout the study. Autopsy revealed no pathological changes. Under the conditions of the study, the acute oral LD50 of the test material was determined to be in excess of 2000 mg/kg bw.

Inhalation

In accordance with Column 2 (adaptation statement) of Annex VIII of Regulation (EC) 1907/2006 (REACH), it is considered justified to omit the acute inhalation toxicity study required under information point 8.5.2 on the basis of exposure considerations. 

Integrated testing strategies for acute toxicity state that determination of the most likely route of exposure needs to take into account not only how the substance is manufactured and handled, including engineering controls and risk management measures, but also the physicochemical properties of the substance.

The nature of the registered substance means that it is not potentially inhalable; the substance has low vapour pressure and therefore is unlikely to be available for inhalation as a vapour. The low water solubility, high molecular weight and the high log Pow value suggest a limited absorption after inhalation.

If any amount of the substance reaches the alveoli, this will be likely phagocytised by macrophages, located into the immune surveillance tissues and broken down in lysosomes and peroxisomes.

Dermal

In accordance with Section 1 of Annex XI of Regulation (EC) 1907/2006 (REACH), it is considered justified to omit the acute dermal toxicity study required under information point 8.5.3 of Annex VII on the basis of exposure considerations. 

The physical state, high molecular weight and high log Pow value obtained, together with the low water solubility, indicate very low potential for dermal absorption. Similarly to mineral oils, deposition in the stratum corneum is expected to occur slowly; however, the substance is not sufficiently water soluble to partition from the stratum corneum into the epidermis.

As dermal absorption cannot be greater than oral absorption, and the acute oral toxicity study revealed no signs of toxicity up to the maximum permissible dose of 2000 mg/kg bw, no toxicity following acute dermal exposure is expected to occur.

Justification for selection of acute toxicity – oral endpoint
Only one study is available.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, and in accordance with Directive 67/548/EEC, the substance does not require classification as no signs of toxicity were noted during the course of the acute oral toxicity study.