Octadecanoic acid, reaction products with 2-amino-2-methyl-1-propanol

Endpoint summary

Description of key information

Based on the results of a read across study, the oral LD50 value of the test substance, C16 -18 AMP is considered to be >2000 mg/kg bw (indicating low acute oral toxicity potential).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From November 27, 2012 to January 24, 2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to section 13 of IUCLID for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

not specified

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: breeder: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 201 g (range: 191 g to 208 g)
- Fasting period before study: yes, during the night before treatment
- Housing: the animals were housed by three from the same group in polycarbonate cages with stainless steel lids (Techniplast 2154, 940 cm2)
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: 04 December 2012 to 26 December 2012.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/kg
- Maximum dose-volume applied: 10 mL/kg

DOSAGE PREPARATION (if unusual): The test substance was administered as a homogenous suspension in the vehicle. Although the test substance was a wax, it was ground to a fine powder, using a mortar and pestle, and then mixed with the required quantity of vehicle. Dose formulations preparations were prepared by the CiToxLAB France Pharmacy extemporaneously on the day of each administration. The dose formulations were stored at room temperature and delivered to the study room in brown flasks.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: The starting dose-level was selected in agreement with the Sponsor, based on available test item toxicity data, no morbidity or mortality was expected to occur at the dose level of 2000 mg/kg. This was therefore chosen as the starting dose-level. After treatment at the starting dose-level, the next dose-level was administered in a sequential manner, under the same conditions to different animals, based on the dose-levels indicated in the flow charts of OECD Guideline No. 423, 17th December 2001, which are equivalent to those of Commission Regulation (EC) No. 440/2008, B.1tris (30 May 2008). Based on the results obtained for groups 1 and 2, a third group was not tested.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females per treatment step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Clinical observations: frequently during the hours following treatment; then once a day
- Body weight: just before treatment on Day 1; then on Days 8 and 15
- Necropsy of survivors performed: yes (macroscopic)

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed in any animals.

Gross pathology:

There were no macroscopic post-mortem observations.

Interpretation of results:

other: Not classifed based on EU CLP Criteria

Conclusions:

Based on the results of the read across study, similar oral LD50 value of >2000 mg/kg bw can be considered for the test substance, C16-18 AMP.

Executive summary:

A study was conducted to determine the acute toxicity of the read across substance, Oleamide MIPA, according to OECD Guideline 423 and EU Method B1, Acute Toxic Class Method, in compliance with GLP. The test substance was administered once by the oral route (gavage) to two groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test substance was prepared in corn oil. Based on available data, the starting dose-level of 2000 mg/kg bw was chosen. After the first assay, as no toxicity was observed, the results were confirmed in three other females. Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on the day of allocation of the animals into groups, then on Days 1, 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No tissues were preserved. No unscheduled deaths occurred during the study and no clinical signs were observed in any animals. When compared to study laboratory historical control data and taking into account the initial body weight values, a lower body weight gain was noted in 1/6 females between days 1 and 8 and in 2/6 females between Days 8 and 15. In addition, an overall lower body weight gain was observed in 1/6 females between Days 1 and 15. The test substance had no effect on the body weight evolution, as these lower body weight gains were considered to be minimal and of fortuitous occurrence. There were no macroscopic post-mortem observations. Under study conditions, the oral LD50 of the test substance, was determined to be >2000 mg/kg bw in rats (Papineau, 2013). Based on the results of the read across study, similar oral LD50 value of >2000 mg/kg bw can be considered for the test substance, C16-18 AMP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline compliant study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

A study was conducted to determine the acute toxicity of the read across substance, Oleamide MIPA, according to OECD Guideline 423 and EU Method B1, Acute Toxic Class Method, in compliance with GLP. The test substance was administered once by the oral route (gavage) to two groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test substance was prepared in corn oil. Based on available data, the starting dose-level of 2000 mg/kg bw was chosen. After the first assay, as no toxicity was observed, the results were confirmed in three other females. Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on the day of allocation of the animals into groups, then on Days 1, 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No tissues were preserved. No unscheduled deaths occurred during the study and no clinical signs were observed in any animals. When compared to study laboratory historical control data and taking into account the initial body weight values, a lower body weight gain was noted in 1/6 females between days 1 and 8 and in 2/6 females between Days 8 and 15. In addition, an overall lower body weight gain was observed in 1/6 females between Days 1 and 15. The test substance had no effect on the body weight evolution, as these lower body weight gains were considered to be minimal and of fortuitous occurrence. There were no macroscopic post-mortem observations. Under study conditions, the oral LD50 of the test substance, was determined to be >2000 mg/kg bw in rats (Papineau, 2013). Based on the results of the read across study, similar oral LD50 value of >2000 mg/kg bw can be considered for the test substance, C16-18 AMP.

Justification for classification or non-classification

Based on the results of an acute oral toxicity read across study, the test substance, C16 -18 AMP does not warrant classification for acute oral toxicity, according to the EU CLP criteria (Regulation 1272/2008/EC).