Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral (OECD 401): LD50 values > 2000 mg/kg bw
Inhalation (OECD 436): LC50 > 5.3 mg/L air
Dermal: no data available

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:
17 Feb - 02 Mar 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
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 GmbH, Sulzfeld, Germany.
- Age at study initiation: Approx. 8 weeks
- Weight at study initiation: males: 269- 273 g, females: 193 - 205 g
- Housing: Individually housed in polycarbonate cages
- Fasting period before study: Over night until 3 h after application
- Diet: ad libitum (RMH-B, Hope Farms, The Netherlands)
- Water: ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 17 Feb 1988 To: 02 Mar 1988.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The dose level was 2000 mg/kg bw and the dose volume (mL/kg bw) used was calculated as follows:

dose (g/kg bodyweight) / density (g/mL) = 2/0.8532 = 2.34 mL/kg (asumming test substance density of 0.8532 g/mL)







Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Toxicity: every second hour on the day of dosing, afterwards daily; body weight were measured weekly
- Necropsy of survivors performed: yes
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 of toxicity were observed up to the end of the observation period.
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
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) and consistent studies from a reference substances with similar structure and intrinsic properties. Read-across is justified based on common functional groups, common precursors/breakdown products and similarities in physicochemical and toxicological properties (refer to endpoint discussion for further details). The selected study is 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.

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:
28 Apr - 12 May 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl:WI(Han)
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: approximately 12 weeks old
- Weight at study initiation: max. ± 20% of the sex mean
- Housing: before exposure: Group housing of five animals per sex per cage in labelled Makrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom); after exposure: Group housing of maximally three animals per sex per cage as described above, except that a paper sheet was introduced into the cage covering the bedding and cage enrichment to prevent suffocation in case of bad health condition. At the end of the Day of exposure the paper sheet was removed.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) except during exposure to the test substance, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 (actual range: 19.8 – 21.4)
- Humidity (%): 40-70 (actual range: 37 - 63)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The design of the exposure chamber is based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983).
- Method of holding animals in test chamber: animal ports
- System of generating particulates/aerosols: An aerosol was generated by nebulization of the test substance by means of a nebulizer (type 950, Hospitak Inc., Lindenhurst, NY, USA)
- Method of particle size determination: Amounts of test substance collected were measured gravimetrically. Subsequently the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD) were determined
- Treatment of exhaust air: From the exposure chamber the test atmosphere was passed through a filter before it was released to the exhaust of the fume hood.
- Temperature, humidity, pressure in air chamber: The temperature of the atmosphere was between 20.8 and 21.2 °C and relative humidity was between 23 and 25%. These conditions were considered appropriate for this relatively short 4 hours exposure duration.

TEST ATMOSPHERE
- Brief description of analytical method used: Samples were drawn through a glass fiber filter (type APFC04700, Millipore, Billerica, MA, USA). The collected amount of test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands).
- Samples taken from breathing zone: yes

VEHICLE
- The test substance was used undiluted.

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMAD and GSD were determined twice, MMAD was 4.0 µm (GSD 2.4) and 5.2 µm (GSD 1.9).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: The target concentration was based on the hazard categories for dust and mists specified in the Globally Harmonized System of Classification of Chemicals (GHS), United Nations, New York and Geneva, 2003.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetrically
Duration of exposure:
4 h
Concentrations:
The mean actual concentration was 5.3 ± 0.3 mg/L. The nominal concentration was 7.1 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 75%. Data obtained from the opacity monitor showed that the aerosol was sufficiently stable.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability: Twice daily; clinical signs during exposure: three times during exposure for mortality, behavioural signs of distress and effects on respiration. Clinical signs after exposure: twice (at 1 and at 3 hours after exposure) on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded: maximum grade 4: grading slight (1) to very severe (4); maximum grade 3: grading slight (1) to severe (3); maximum grade 1: presence is scored (1); body weights Days 1 (pre-administration), 2, 4, 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed (the method used was not intended to calculate a LC50 value).
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.3 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred.
Clinical signs:
other: Hunched posture was observed in all animals 1 and 3 hours after exposure. No clinical signs were noted during exposure.
Body weight:
Body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study.
Gross pathology:
No abnormalities were observed at macroscopic post mortem examination of the animals.

The inhalatory 4-h LC50value of isopropyl laurate in Wistar rats was found to exceed 5 mg/L.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional groups, common precursors/breakdown products and similarities in physicochemical and toxicological properties (refer to endpoint discussion for further details). The selected study is 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.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are no data available on the acute toxicity of isodecyl pivalate (CAS 60209-82-7). In order to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview of acute toxicity

CAS

Chemical name

Molecular weight

Acute toxicity oral

Acute toxicity inhalation

Acute toxicity dermal

60209-82-7 (a)

Isodecyl pivalate

ca. 242

RA: CAS 10233-13-3
RA: 110-27-0

RA: CAS 10233-13-3

Waiving

10233-13-3 (b)

Isopropyl laurate

ca. 242

Experimental result:
LD50 > 5000 mg/kg bw

Experimental result:
LC50 > 5.3 mg/L air

--

110-27-0

Isopropyl myristate

270.46

Experimental result:
LD50 > 2000 mg/kg bw

--

--

(a) Substances subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for isodecyl pivalate (CAS 60209-82-7). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Acute oral toxicity

CAS 10233-13-3

An acute oral toxicity study (limit test) with isopropyl laurate (CAS 10233-13-3) was performed according a protocol similar to OECD 401 (Supporting, Starinerie, 1991). A group of 5 female NMRI EOPS mice received single oral doses of 5000 mg/kg bw. No mortalities were observed during the 6-day study period. No signs of clinical toxicity were reported. The animals showed the expected gain in body weight. The acute oral LD50 in mice was found to be > 5000 mg/kg bw.

CAS 110-27-0

An acute oral toxicity study (limit test) was performed with isopropyl myristate (CAS 110-27-0) according to OECD Guideline 401 (Key, Croda, 1988). Groups of 5 male and female fasted Wistar rats received single oral gavage doses of 2000 mg/kg bw. The animals were observed for 14 days after administration. No mortalities occurred. No signs of clinical toxicity were reported. The acute oral LD50 was > 2000 mg/kg bw.

Acute inhalation toxicity

CAS 10233-13-3

An acute inhalation study was performed with isopropyl laurate (CAS 10233-13-3) according to OECD 436 (acute toxic class method) (Key, MHM, 2010). 3 male and 3 female Crl:WI(Han) rats were exposed to an analytical concentration of 5.3 mg/L of the test substance for 4 hours nose-only in an exposure chamber based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). An aerosol was generated by nebulization of the test substance using a nebulizer. No mortalities were reported during the exposure or within the 14-day observation period. Hunched posture was observed in all animals 1 and 3 hours after exposure. No clinical signs were noted during exposure and the body weight gain was within the range expected for rats of this strain and age. No abnormalities were found during the macroscopic post-mortem examination of the animals. The inhalatory 4 h LC50value of isopropyl laurate in Wistar rats was found to exceed 5.3 mg/L.

Acute dermal toxicity

This information is not available.

Conclusions for acute toxicity

No acute toxicity data is available for isodecyl pivalate (CAS 60209-82-7). However, no mortality was observed in studies performed with the structurally related substances isopropyl laurate (CAS 10233-13-3) and isopropyl myristate (CAS 110-27-0) (Supporting, Stearinerie, 1991; Key, Croda, 1988). The oral LD50 was > 5000 mg/kg bw. The LD50 for inhalation of > 5.3 mg/L was derived from the source substance isopropyl laurate (CAS 10233-23-3) (Key, MHM, 2010).

A dermal LD50 was not derived as no dermal exposure is expected. Furthermore, the physicochemical properties of the substance (molecular weight: 242.41 g/mol, log Pow > 3, water solubility < 0.05 mg/L) are in a range that anticipate a lower dermal absorption rate than via the oral and inhalation route. Since the substance is neither acute toxic by the oral route (LD50 > 2000 mg/kg bw based on read-across) nor skin or eye irritating and there are no indications for a skin sensitising potential, it is unlikely that acute dermal exposure would lead to toxic effects at dose levels lower than the oral LD50. Therefore, testing for acute toxicity by the dermal route is also deemed scientifically unjustified in accordance with Annex XI, Section 1.2 of Regulation (EC) 1907/2006, based on the weight of evidence from the available physicochemical and toxicological data documented in the technical dossier and the Chemical Safety Report. Hence, further testing on vertebrate animals for this property shall be omitted.


Justification for classification or non-classification

Based on read-across from the structurally similar substances, the available data on oral and inhalation toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.

There are no data available on acute dermal toxicity.