Glycerol monomyristate

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg bw

Dermal: LD50 > 2000 mg/kg bw

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:

13 Mar - 27 Mar 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study with accepatble restrictions. Lack of details on test material.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

lack of details on test material

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

other: NMRI-Han albino mice

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Test Facility breeding, Blanquefort, France
- Age at study initiation: 5 weeks
- Weight at study initiation: 19.4 - 21.9 g
- Fasting period before study: animals were fasted overnight prior to administration.
- Housing: 5 animals per cage in polypropylene cages with stainless steel lid on wood shavings bedding.
- Diet: sterilized pelleted diet (UAR, Epinay sur Orge, France), ad libitum
- Water: tap water (periodically analyzed), ad libitum
- Acclimation period: none, as breeded in test facility

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50 ± 20
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100 mg/mL
- Amount of vehicle (if gavage): 20 mL/kg bw
- Justification for choice of vehicle: T,he vehicle was chosen according to the nature of the test substance and producing no painful effect in agreement with the rules of animal ethics.

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

DOSAGE PREPARATION: The test substance was crushed and homogenized with a pestle in a mortar, and then diluted in corn oil.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of clinical observations: animals were observed daily
- Frequency of weighing: on Days 1, 4, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Slight piloerection was observed in male and female animals within the first h after test substance application. No other clinical signs of toxicity occured.

Gross pathology:

No abnormalities were observed in all treated animals.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study, and is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

16 Dec - 30 Dec 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No. 8147, November 2000

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar Crl:WI (Han) (outbred, SPF-Quality)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 277 - 304 g (males) and 184 - 202 g (females)
- Housing: individually housed in labelled Macrolon cages (Mlll type) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Nonham Mill Ltd), Surrey, UK).
- Diet: pelleted rodent diet (SM R/M-Z from SSNlFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: approx. 25 cm² on the dorsal area (males) and 18 cm² (females), respectively
- % coverage: 10%
- Type of wrap if used: dressing consisting of a surgical gauze patch (Surgy 1D, Laboratoires Stella sa., Liege, Belgium), successively covered with aluminum foil and Coban elastic bandage (3M, St. Paul, MN, USA.). A piece of Micropore tape (3M, St. Paul, MN, USA) was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed with tap water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
- Concentration (if solution): 200 mg/mL

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed twice daily for mortality and viability, and individual body weights were determined at Day 1 (pre-administration), 8 and 15; clinical signs were determined at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Flat posture was noted among all animals on Day 1. Chromodacryorrhoea was observed in 3/5 males and in 2/5 females on Day 1. Ptosis was determined in 2/5 males and in 4/5 females. 3/5 females showed restless behaviour on Day 1. Scales and scabs of the rig

Gross pathology:

Necropsy revealed no substance-related findings.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

CLP: not classified
DSD: not classified

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 Mar - 26 Mar 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study with acceptable restrictions. Lack of test material details.

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

lack of test material details

GLP compliance:

yes

Remarks:

*

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann GmbH, Borchen, Germany
- Weight at study initiation: 179 g (males) and 143 g (females)
- Housing: animals were housed individually in Makrolon cages type II with soft wood bedding
- Diet: Altromin 1324 (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 51
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 cm x 4 cm clipped skin of the dorsal area of the trunk
- Type of wrap if used: The test material was held in contact with the skin with gauze and polyethylene sheet and leukosilk bandage and acrylastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was washed off
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: several times on day of application, thereafter twice a day
- Frequency of observations and weighing: before administration and on Days 2, 7 and 14.
- Necropsy of survivors performed: yes, after 14 days from all treated animals
- Other examinations performed: daily skin examination

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs were observed up to the end of the 14-day observation period.

Gross pathology:

Necropsy and histopathological examination revealed no substance-related findings. One male and two female animals showed a reddening of the ileum mucosa, not treatment-related.

Other findings:

No local skin irritation observed.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable studies (Klimisch score 1 or 2) from reference substances with similar structure and intrinsic properties. Read-across is justified based on structural similarity and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details). The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Acute oral toxicity

The acute oral toxicity of Glycerol monomyristate (CAS 27214-38-6) was investigated in a GLP-conform study performed according to OECD guideline 401 (Stearinerie, 2000). Groups of 5 NMRI-Han albino mice per sex received the undiluted test substance via gavage at a limit dose of 2000 mg/kg bw. No mortality was observed up to the end of the14-day observation period. Clinical signs involved slight piloerection in male and female animals within the first hour after test substance application. No other clinical signs of toxicity occurred. All animals showed the expected gain in body weights during the study. Macroscopic examination of animals at termination did not reveal any treatment-related findings. Based on the results of the study, the oral LD50 value for male and female NMRI-Han albino mice is > 2000 mg/kg bw.

Acute dermal toxicity

Justification for read-across

Data on the acute dermal toxicity of Glycerol monomyristate (CAS 27214 -38 -6) are not available. The assessment of acute dermal toxicity was therefore based on data from source substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

The acute dermal toxicity of Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates (CAS 91052 -13 -0) was investigated in a limit test according to OECD guideline 402 and in compliance with GLP (Riken, 2010). In this study, 5 male and 5 female rats were treated with the test substance at a dose of 2000 mg/kg bw. The test substance was dissolved in polyethylene glycol at a concentration of 200 mg/mL and applied onto the shaved skin of the test animals (10 mL/kg bw) for 24 h under occlusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No mortalities occurred and body weight gain of all animals was within the normal range during the whole study period. Flat posture was noted in all animals on Day 1. On the same day, chromodacryorrhoea was observed in 3/5 males and in 2/5 females. Ptosis was seen in 2/5 males and in 4/5 females, and 3/5 females showed restless behaviour on Day 1. Scales and scabs of the right flank and/or treated skin were observed among 3/5 males and 1/5 females between Days 4 and 15. At necropsy, no substance-related findings were noted. Therefore, the LD50 in male and female rats is > 2000 mg/kg bw.

The acute dermal toxicity of Glycerides, C16-18 and C18-hydroxy mono- and di- (CAS 91845 -19 -1) was tested in accordance with EU method B.3 and in compliance with GLP (BASF, 1985). The study was performed as a limit test in rats (5 males and 5 females) at a dose level of 2000 mg/kg bw. The test substance was applied unchanged to the clipped skin of the test animals for 24 h under occlusive conditions. After removal of the test substance, animals were observed for a period of 14 days. No mortalities and no local dermal signs were noted during the course of the study. No clinical signs of toxicity were observed. Body weight gain was within the normal range in males and females during the whole study period. Necropsy and histopathological examination revealed no substance-related findings. One male and two female animals showed a reddening of the ileum mucosa, which was not considered to be related to treatment. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

Overall conclusion for acute toxicity

The reliable acute toxicity data available for the target and/or source substances indicate a very low level of acute toxicity following both the oral and dermal exposure, as LD50 values were greater than the currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, Glycerol monomyristate (CAS 27214 -38 -6) is not expected to be hazardous following acute exposure.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that "substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Glycerol monomyristate, data will be generated from data available for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

The available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.