Fatty acids, C16 and C18-unsatd., triesters with trimethylolpropane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

other: data sharing dispute

Adequacy of study:

key study

Study period:

25 Jun - 26 Jul 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see remarks

Remarks:

GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Justification for type of information:

Guidance on registration Reference: ECHA-16-G-06-EN Publ.date:November 2016
Practical guide 2: How to report weight of evidence - Reference: ECHA-10-B-05-EN Publ.date: 24/03/2010
"Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008)

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 category concept is applied to the polyol esters, data gaps will be filled by interpolation, as part of a read across approach from a representative category member(s) to avoid unnecessary animal testing. Additionally, once the category concept is applied, substances will be classified and labelled on this basis.Therefore, based on the group concept, all available data on repeated dose toxicity do not meet the classification criteria according to Regulation.
See Category Justification Document Point enclosed at 13.2

Cross-reference

Reason / purpose for cross-reference:

other: weight of evidence

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

other: data sharing dispute

Adequacy of study:

weight of evidence

Study period:

22 Mar - 05 Apr 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions (only few data on test item and animal husbandry were given)

Justification for type of information:

Guidance on registration Reference: ECHA-16-G-06-EN Publ.date:November 2016
Practical guide 2: How to report weight of evidence - Reference: ECHA-10-B-05-EN Publ.date: 24/03/2010
"Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008)

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 category concept is applied to the polyol esters, data gaps will be filled by interpolation, as part of a read across approach from a representative category member(s) to avoid unnecessary animal testing. Additionally, once the category concept is applied, substances will be classified and labelled on this basis.Therefore, based on the group concept, all available data on repeated dose toxicity do not meet the classification criteria according to Regulation.
See Category Justification Document Point enclosed at 13.2

Reason / purpose for cross-reference:

other: weight of evidence

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

(No details on test material and limited data on animal husbandry)

GLP compliance:

not specified

Test type:

other: standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Alpk:APfSD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Alderly Park, Cheshire, UK
- Age at study initiation: approx. 7 weeks

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
- Source and rate of air: dried and filtered air
- System of generating aerosols: glass concentric jet atomiser
- Method of particle size determination: Marple Cascade Impactor
- Temperature, humidity, pressure in air chamber: 20 L/min

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrically
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.51 µm/2.51

Analytical verification of test atmosphere concentrations:

yes

Remarks:

particulate concentrations of the test atmospheres close to the animals breathing zone were measured gravimetrically

Duration of exposure:

ca. 4 h

Concentrations:

5.0 mg/L (nominal)
5.10 mg/L (analytical)

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: animals were observed for gross clinical abnormalities during exposure and were checked daily thereafter. A detailed examination was conducted after exposure on day 1 and on consecutive days, up to and including day 15. Individual body weights were recorded on Day 1 and Days 2, 3, 8 and day 15.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.1 mg/L air (analytical)

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for

Body weight:

No effect on body weight was noted.

Gross pathology:

Necropsy and histopathological examination revealed no substance-related findings.

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Remarks:

THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol

EC Number:

272-469-1

EC Name:

Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol

Cas Number:

68855-18-5

IUPAC Name:

68855-18-5

Specific details on test material used for the study:

- Name of test material (as cited in study report): Heptanoic acid diester of neopentylglycol
- Physical state: clear colourless liquid
- Analytical purity: > 99%
- Purity test date: 2011-10-10
- Lot/batch No.: 595859
- Expiration date of the lot/batch: 2013-10-08
- Storage condition of test material: at room temperature, in the dark

Test animals

Species:

rat

Strain:

other: RccHanTM:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200-350 g
- Housing: animals were housed in groups of up to 3/sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes (Datesand Ltd, Cheshire, UK) and provided with environmental enrichment items (wooden chew blocks and cardboard “fun tunnels” (Datesand Ltd, Cheshire, UK)).
- Diet: Harlan 2014C Rodent Diet (Harlan Laboratories UK Ltd, Oxon, UK), ad libitum (with the exception of the exposure period)
- Water: mains drinking water, ad libitum (with the exception of the exposure period)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

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: cylindrical exposure chamber (ADG Developments Ltd, Hitchin, UK)
- Exposure chamber volume: 30 L
- Method of holding animals in test chamber: each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring. Prior to the day of exposure, each rat was acclimatised for approx. 2 h to the tapered polycarbonate restraining tube.
- Source and rate of air: filtered air supplied from an oil-free compressor at 60 L/min
- System of generating particulates/aerosols: glass concentric jet nebuliser (Radleys, Saffron Walden, UK)
- Method of particle size determination: Marple Personal Cascade Impactor (Westech, IS Ltd, Beds., UK), consisting of 6 impactor stages (7.8, 5.8, 3.6, 1.4, 0.74 and 0.34 µm) with stainless steel collection substrates and a back-up glass filter, housed in an aluminium sampler
- Treatment of exhaust air: the extract from the exposure chamber passed through a ‘scrubber’ trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature, humidity, pressure in air chamber: 19-20 °C, 71-72%, negative

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric filter analysis was used to determine the actual concentration of the aerosol. The test atmosphere was sampled at regular intervals (approx. every 10-15 min) during the exposure period. A weighed glass fibre filter was placed in a filter holder and temporarily sealed in a vacant port of the exposure chamber. A known quantity of the exposure chamber concentration was drawn through the filter using a vacuum pump. After sampling, the filter was dried in a desiccator under reduced pressure at 19-21 °C for ca. 24 h and weight thereafter.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see Table 1 and 2 under "Any other information on materials and methods incl. tables"
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.42 µm/2.56 µm

CLASS METHOD
- Rationale for the selection of the starting concentration: a target concentration of 5 mg/L was chosen based on a preliminary sighting study in two rats treated with a mean achieved test atmosphere concentration of 2.14 mg/mL. In this experiment, no significant effects were observed in the animals after an exposure period of 4 h.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric

Duration of exposure:

4 h

Concentrations:

5.22 mg/L (mean achieved concentration)
13.5 mg/L (nominal concentration)

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: animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for over 14 days. Individual body weights were recorded on arrival, prior to treatment and on Days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes, full external and internal observation. Detailed macroscopic examination of the respiratory tract was performed to determine signs of irritancy or local toxicity.
- Other examinations performed: clinical signs, body weight

Statistics:

Mean values and standard deviations of the mean achieved atmosphere concentrations were determined.

Results and discussion

Preliminary study:

In a preliminary sighting study, 2 rats treated with a mean achieved test atmosphere concentration of 2.14 mg/mL (target: 2 mg/mL) showed no significant effects after an exposure period of 4 h. Clinical signs during exposure included wet fur and an increased respiratory rate. In addition, hunched posture and pilo-erection were observed directly after exposure and 1 h thereafter. The increase in respiratory rate was still present until Day 3 post-exposure. One day later, all animals were free of any clinical symptoms. No macroscopic findings were observed at necropsy. Thus, a starting concentration of 5 mg/mL was chosen for the main experiment.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.22 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Signs of hunched posture and pilo-erection were seen in test animals for a short period after removal from the exposure chamber. Wet fur was recorded during the exposure period and for a short time period thereafter which were considered to be associated

Body weight:

All animals showed the expected body weight gain during the study, except for one female which did not gain weight during the 14-day observation period. In addition, one male exhibited a slight loss in body weight on the first day of exposure.

Gross pathology:

At necropsy, no macroscopic abnormalities were observed in the treated animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified
DSD: not classified