Methyl undec-10-enoate

Endpoint summary

Description of key information

Acute oral : a study according to GLP guideline study (NF T03-021), LD50 = 1563 mg/kg bw (males and females)
Acute dermal : a study according GLP guideline study (OECD 402), LD0 > 2000 mg/kg bw (males and females)
Acute inhalation : a study according GLP guideline study (OECD 403), LD50 = 3.76 mg/l = 3.76 g/m3 (males and females)

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:

1984-05-17 till 1984-10-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study.

Qualifier:

according to guideline

Guideline:

other: French Guideline NF T 03.021 from 1980

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

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 France (76410, Saint Aubin les Elbeuf - France)
- Age: no data
- Weight at study initiation: 199g (males), 187g (females)
- Fasting period before study: no data
- Housing: 5 animals of same sex were housed in one polycarbonate cage with stainless top
- Diet (e.g. ad libitum): pelleted rat diet "Expanded SQC" (Special Diets Services Ltd, Witham, Essex, England)
- Water (e.g. ad libitum): potable water filtered through Millipore membrane, ad libitum
- Acclimation period: min. 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C ± 3°C
- Humidity (%): 50 % ± 20%
- Air changes (per hr): air was not recycled, air was filtered
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

IN-LIFE DATES: From: 1984-05-17 To: 1984-07-31

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE: not applicable


MAXIMUM DOSE VOLUME APPLIED: 5.7 ml/kg


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

Doses:

620, 1240, 1860, 2570 mg/kg body weight (pre-test 5000 mg/ kg bw)

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations frequently directly after test item application, and twice a day thereafter; body weight measurement just before test item application, and at days 4, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

no statistics applied

Preliminary study:

5000 mg/kg bw: animals are in state of coma one hour after test item application.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 563 mg/kg bw

95% CL:

>= 1 225 - <= 1 875

Mortality:

Number and date of deaths at each dose:
At 620 mg/kg: no death
At 1240 mg/kg: 2 dead animals on day 1
At 1860 mg/kg: 8 dead animals 3 hours after treatment
At 2570 mg/kg: 9 dead animals 3 hours after treatment

Clinical signs:

other: At 620 mg/kg: no symptom At 1240 mg/kg: hypokinesia on day 1, then no symptom At 1860 mg/kg: hypokinesia and sedation on day 1, pilo-erection from D1 to D6, then no symptom. At 2570 mg/kg: sedation on day 1, then no symptom. One male went into a coma

Gross pathology:

Due to absence of any macroscopally visible lesions, no further histopathologic investigations

Other findings:

- Organ weights: no abnormalities reported
- Histopathology: not investigated (see above)
- Potential target organs: not investigated
- Other observations:

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: other: Guidance to regulation (EC) No 1272/2008 on CLP of substances and mixtures.

Conclusions:

LD50 is assessed at 1563 mg/kg (95% CL 1225-1875 mg/kg). Symptoms start to appear within 15 min after treatment at the dose of 1248 mg/kg and above (hypokinesia, sedation and coma). Mortality appears 3 hours after treatment, until day 1. Acc. to UN-GHS, the test item UNDECYLENATE DE METHYLE is classified as acute toxic (oral) category 4.

Executive summary:

LD50 is assessed at 1563 mg/kg (95% CL 1225-1875 mg/kg). Symptoms start to appear within 15 min after treatment at the dose of 1248 mg/kg and above (hypokinesia, sedation and coma). Mortality appears 3 hours after treatment, until day 1. Acc. to UN-GHS, the test item UNDECYLENATE DE METHYLE is classified as acute toxic (oral) category 4.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 563 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-02-23 till 1999-07-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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: Charles River, Wiga, Sulzfeld , FRG
- Age at study initiation: no data
- Weight at study initiation: Just before the start of the respective exposures, the mean body weights of the male and female rats were 246 g and 181 g, respectively .
- Fasting period before study: no data
- Housing: 5 by sex per cage.
- Diet (e.g. ad libitum): Institute's stock diet for rats ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: Total duration of the acclimatization period (including quarantaine ) was 21 (group A ) , 9 (group B ) , 10 (group C ) or 14 days (group D


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):


IN-LIFE DATES: From: 1993-02-02 (gropu A) 1993-03-31 (groups B, C, D) To: 1993-04-13

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Animals w ere exposed to the test atmosphere in a nose-only inhalation chamber which w as a modification of the chamber manufactured by ADG Developments LTD., Codicote, Hitchin, U.K.. The chamber consists of a cylindrical polypropylene column, surrounded by a transparent PVC cylinder. The polypropylene column had a volume of 50 liter, consisting of a top assembly with the entrance of the chamber, underneath the rodent tube section and at the bottom the base assembly with the exhaust port.
- Exposure chamber volume: the polypropylene column had a volume of 50 liter
- Method of holding animals in test chamber: The animals were secured in plastic animal holders (Battelle) , positioned radially through the outer cylinder around the central aluminium column.
- Source and rate of air: Before the start of the exposure, the rate of airflow through the generation device (see Section 2.4) was established at its pressure used. The pressure settings were recorded a t regular intervals (ca . each hour), and they did not change during the exposure period ( 1.0 bar ; 30 l / min ) .
- Method of conditioning air: The amount of humidified dilution air was recorded at the same time using calibrated rotameters. Bypass air was 24 (group A ) , 50 (group B ) , 30 (group C) and 32 l/min (group D) . In this way, the total exposure air flow was monitored indirectly through the aerosol generation system and was 54 (group A ) , 80 (group B ) , 60 (group C ) and 62 l/min (group D ).
- System of generating particulates/aerosols: Test atmospheres were generated by atomizing the test material into small droplets by using a compressed air driven nebulizer of the Institute's design. The nebulizer consisted of an atomizer and a glass jar, containing the test material. The atomizer coded DR 011, was purchased from Lechler (Germany). The nebulizer was operated a t a pressure of 1.0 bar. During operation, the test material was drawn through a sucktion pipe to the atomizer. The generated spray was blown against a baffle which was fitted approximately 8 cm below t h e nozzle
orifice to remove the larger droplets. The impacted test material was drained back into the test material supply at the bottom of the jar. The resulting aerosols were passed from the glass jar to the inlet of the exposure unit where it was diluted with humidified pressurized air. From there the test atmosphere was directed downward through the mixing chambers towards the animal noses.
- Method of particle size determination: carried out once per exposure using an 11-stage cascade impactor
- Treatment of exhaust air: At the bottom of the unit the test atmosphere was exhausted
- Temperature, humidity, pressure in air chamber: temperature between 19.7 and 25.0 °C, relative humidity between 30 and 72 %, pressure 1.0 bar


TEST ATMOSPHERE
- Brief description of analytical method used:
- Gravimetrical analysis:
The actual concentration of methyl undecylenate in the test atmosphere was determined once per hour by means of gravimetric analysis. Representative samples were obtained by passing 10 l test atmosphere at ca. 5 l/min through fiber glass filters (Sartorius) . Before and after sampling each filter was weighed. The actual concentration was calculated by dividing the weight difference before and after sampling by the amount of air sampled.
- GC analysis
GC anallysis was additionally carried out t o determine the amount of methyl undecylenate in the test atmosphere. Representative samples were obtained by passing 5-8 l test atmosphere a t 0.75 l/min through one impinger filled with acetone (p.a.). In preliminary experiments it was shown that one
impinger was sufficient since no test material was observed in the second impinger which were connected in tandem. The content of each impinger was quantitatively t ransferred to 50 ml volumetric flasks. Each impinger and the sampling tube were rinsed with the solution; each rinsing was transferred to the volumetric flasks as well.
- Samples taken from breathing zone: yes


VEHICLE (no vehicle used)
- Composition of vehicle (if applicable):
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Particle size distributions are given i n Table 2 of the original study report. Particle size measurement showed that at least 95 % of the particles had an aerodynamic diameter between 1.0 and including 4.2 µm.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:
The study was started with one group of 5 rats per sex which was exposed nose-only for 4 hours at a target concentration of at least 5 g/m³. Since
all animals died at that concentration, three more groups were exposed. During the assay proper, nominal concentrations were 2.6, 3.7, 4.5 and 5.9 g/m³, resp.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC analysis

Duration of exposure:

ca. 4 h

Concentrations:

2.67, 3.72, 4.54 or 5.48 g/m³ (measured)

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were visually inspected just before exposure, for reactions to treatment during the exposure, shortly after exposure, and a t l e a s t once daily during the observation period. Body weights were recorded just prior to exposure (day 0) , on days 7 and 14 and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All rats were autopsied and examined for gross pathological changes.

Statistics:

The statistical program used was based on Finney (Finney, D. J., Probit Analysis, Cambridge Univ. Press, 3rd. ed. 1971).

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 3.76 mg/L air (analytical)

95% CL:

>= 3.25 - <= 4.1

Exp. duration:

4 h

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 3.58 mg/L air (analytical)

95% CL:

>= 2.92 - <= 4.07

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 3.94 mg/L air (analytical)

95% CL:

>= 3.34 - <= 4.46

Exp. duration:

4 h

Mortality:

Several rats were found dead during the last hour of exposure, viz. all rats exposed to 5.48 g/m3 (group A), 4 of 5 males and 4 of 5 females exposed to 4.54 g/m3 (group C), and 3 of 5 males and 1 of 5 females exposed to 3.72 g/m3 (group D). In addition, one male exposed to 4.54 g/m3 and one female exposed to 3.72 g/m3 were found dead within two hours after exposure stop.

Clinical signs:

other: Irregular breathing was observed in all rats exposed to 2.67 g/m3 (group B) and 4.54 g/m3 (group C ) during the third hour of exposure, and in all rats exposed to 3.72 g/m3 (group D) during the second and third hour of exposure. Shallow breathing was seen

Body weight:

In surviving rats, no abnormalities in body weight gain were observed except in most female rats exposed to 2.67 g/m3 (group B) that showed only
marginal body weight gain during the second week of observation.

Gross pathology:

Animals that died during or shortly after exposure showed numerous abnormalities. Stiffly closed eyes were seen in several rats. Two male rats of each group exposed to 3.72, 4.54 or 5.48 g/m3 showed presence of white substance in the eye chamber of both eyes; one male and one female exposed to 5.48 g/m3 showed the same finding but in one eye chamber only. Upon autopsy, almost all rats showed dark and swollen livers and dark discoloured, occasionally blood-containing, lungs. In addition, upon removal of the organs (such as liver) in animals exposed to the highest concentration, much oedema was observed as confirmed by the presence of large amounts of fluid. Occasional findings consisted of swollen blood vessels in various organs such as stomach, caecum, intestines, testes and/or seminal vesicles.
At terminal sacrifice of the surviving rats 14 days after exposure, no abnormalities were observed.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: other: Guidance to Regulation (EC) No 1272/2008 on CLP of substances and mixtures

Conclusions:

For the combined male and female data, the 4-hour LC50 value was 3.76 g/m3 for test item methyl undecylenate. Acc. to the old EU classification and labelling system 67/548/ECC, the test item is classified as R20, Xn, harmful by inhalation. Acc. to the new GHS system, hazard class and category acute tox. inhal. 4 would apply, hazard statement "harmful if inhaled, hazard statement no. 318.

Executive summary:

The aim of the present study was to determine the 4 -hour LC50 of methyl undecylenate. Methyl undecylenate was studied by nose-only exposure of four groups of five males and five females rats each to test atmosphere containing 2.67, 3.72, 4.54, or 5.48 g methyl undecylenate per m3. Nominal concentrations were 2.6, 3.7, 4.5 and 5.9 g/m3, respectively. The 4 -hour LC50 value was calculated using the probit function, as described by Finney (1971). For the combined male and female data, the 4-hour LC50 value was 3.76 g/m3 with 95%-confidence limits of 3.25 and 4.10 g/m3. When separated for sexes, the 4 -hour LC50 values (and 95%-confidence limits ) were 3.58 (2.92 -4.07) and 3.94 (3.34-4.46) g/m3 for males and females, respectively, indicating higher, though statistically insignificantly, susceptibility to methyl undecylenate for male rats .

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

3 760 mg/m³ air

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:

1999-03-20 till 1999-08-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline-conform study under GLP without deviations

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Crkdo, L'Arbresle, France.
- Age at study initiation: 8 weeks
- Weight at study initiation: 248 +/- 8 g for the males and 236 +/- 15 g for the females
- Fasting period before study: no data
- Housing: During the treatment period, the animals were housed individually in polycarbonate cages (35.5 cm x 23.5 cm x 19.3 cm). Each cage contained dust-free sawdust.
- Diet (e.g. ad libitum): All the animals had free access to A04 C pelleted diet (UAR, Villemoisson-sur-Orge, France)
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: at least 5 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2°C
- Humidity (%): 30 to 70%
- 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: From: 1999-03-24 To: 1999-04-07

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 cm x 6 cm for the females and 5 cm x 7 cm for the males
- % coverage: approximately 10% of the body surface of the animals
- Type of wrap if used: hydrophilic gauze pad


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No residual test substance was observed at removal of the dressing.
- Time after start of exposure: not applicable


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable

Duration of exposure:

24 h

Doses:

2000 mg/kg body weight

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: observation of the animals was made at least once a day until day 15. The animals were weighed individually just before administration of the test substance on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

no statistics applied

Preliminary study:

As the test substance was anticipated to be non-toxic at 2000 mg/kg, a limit test was performed by application of 2000 mg/kg of the test substance to one group of ten animals

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Mortality:

No death occurred during the study.

Clinical signs:

other: No clinical signs and no cutaneous reactions were observed during the study.

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: Guidance to Regulation (EC) No 1272/2008 on CLP of substances and mixtures

Conclusions:

Under the given experimental conditions, the dermal LDo of the test substance UNDECYLENATE DE METHYLE (batch No. 9810006) is equal to or higher than 2000 mg/kg in rats.

Executive summary:

The object of the study was to determine the acute dermal toxicity of test item UNDECYLENATE DE METHYLE according to OECD (No. 402, 24th February 1987) and EC (92/69/EEC, B.3, 31st July 1992) guidelines. Test subjects were male and female rats. Since the test substance was anticipated to be basically non-toxic, a fixed-dose limit test was carried out with a test item concentration of 2000 mg/kg. Under the given experimental conditions, the dermal LDo of the test substance UNDECYLENATE DE METHYLE (batch No. 9810006) is equal to or higher than 2000 mg/kg in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Oral acute :

LD50 is assessed at 1563 mg/kg (95% CL 1225-1875 mg/kg). Symptoms start to appear within 15 min after treatment at the dose of 1248 mg/kg and above (hypokinesia, sedation and coma). Mortality appears 3 hours after treatment, until day 1.

Dermal acute :

The object of the study was to determine the acute dermal toxicity of test item methyl undec-10-enoate.

Test subjects were male and female rats. Since the test substance was anticipated to be basically non-toxic, a fixed-dose limit test was carried out with a test item concentration of 2000 mg/kg. Under the given experimental conditions, the dermal LDo of the test substance methyl undec-10 -enoate is equal to or higher than 2000 mg/kg in rats. Inhalation acute :

The aim of the present study was to determine the 4 -hour LC50 of methyl undecylenate. Methyl undecylenate was studied by nose-only exposure of four groups of five males and five females rats each to test atmosphere containing 2.67, 3.72, 4.54, or 5.48 g methyl undecylenate per m3. Nominal concentrations were 2.6, 3.7, 4.5 and 5.9 g/m3, respectively. The 4 -hour LC50 value was calculated using the probit function, as described by Finney (1971). For the combined male and female data, the 4-hour LC50 value was 3.76 g/m3 with 95%-confidence limits of 3.25 and 4.10 g/m3. When separated for sexes, the 4 -hour LC50 values (and 95%-confidence limits ) were 3.58 (2.92 -4.07) and 3.94 (3.34-4.46) g/m3 for males and females, respectively, indicating higher, though statistically insignificantly, susceptibility to methyl undecylenate for male rats .

Justification for classification or non-classification

Oral acute :

Acc. to regulation EC No. 1272/2008 and the EU 67/548/ECC, methyl undec-10-enoate is classified as acute toxic (oral) category 4 / R22.

Justification : 200-300 < LD50 < 2000 mg/kg bw

Dermal acute :

According to the EU Directive 67/548/EEC and the Regulation EC no.1272/2008, methyl undec-10-enoate is not classified for acute dermal toxicity.

Justification : LD0 > 2000 mg/kg bw.

Inhalation acute :

Methyl undec-10-enoate is classified as acute toxic category 4 (inhalation) in the new CLP regulation system (regulation EC No.1272/2008). In the EU 67/548/ECC system the classification would be R20, Xn, harmful. Justification : 1.0 < LC50 < 5.0 mg/l (for mists)