Poly[oxy(methyl-1,2-ethanediyl)], .alapha.,α'-(2,2-dimethyl-1,3-propanediyl)bis[ω-[(1-oxo-2-propenyl)oxy

Endpoint summary

Description of key information

Acute studies are available for all three routes of exposure. No mortality was observed in these studies performed according to the OECD guideline.
Propoxylated neopentylglycol diacrylate is considered to be not harmful or toxic after acute exposure (oral, dermal and inhalation route).

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:

From July 28 to August 14, 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

yes

Remarks:

highest temperature recorded was 26 °C

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: Harlan U.K. Ltd, Oxon, England.
- Age at study initiation: Approximately 5-7 weeks
- Weight at study initiation: 122-149 g
- Fasting period before dosing: Overnight
- Fasting period after dosing: 4 h
- Housing: Up to 5 rats/sex in metal cages
- Diet: Standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet), ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21-26 °C
- Humidity: 39-58 %
- Photoperiod: 12 h dark / 12 h artificial light

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- MAXIMUM DOSE VOLUME APPLIED: 3.147 mL/kg bw in preliminary study and 4.916 mL/kg bw in main study
- DOSAGE PREPARATION: Test substance was administered as supplied (specific gravity 1.017).
- Rationale for the selection of the dosage for main study: Dose was selected based on preliminary study conducted on 1 rat/sex/dose at 3200 mg/kg bw and animals were observed for 7 days.

Doses:

- Preliminary study: 3200 mg/kg bw
- Main study: 5000 mg/kg bw

No. of animals per sex per dose:

- Preliminary study: 1
- Main study: 5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: At least twice daily
Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1; subsequently twice daily for 14 days, with the exception of the day of study termination (Day 15)-morning only.
Bodyweight was recorded on Days 1 (prior to dosing), 8 and 15 for main study.
- Necropsy of survivors performed: Yes, all animals were killed by carbon dioxide asphyxiation at study termination (Day 15). All animals were subjected to a macroscopic examination.

Statistics:

None

Preliminary study:

- No mortality was observed.
- Clinical signs: Piloerection, hunched posture, pallid extremities, increased salivation, abnormal faeces and ungroomed appearance, seen in both rats.
- Bodyweight gain for both rats was considered satisfactory.
- No macroscopic abnormalities were observed in either animal at the terminal necropsy on Day 8.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed at 5000 mg/kg bw.

Clinical signs:

other: - Piloerection was observed in all rats within 4 minutes of dosing. This sign persisted and was accompanied in rats later on Day 1 and/or at later intervals during the study by increased salivation, abnormal faeces and ungroomed appearance, seen in all ra

Gross pathology:

- No macroscopic abnormalities were observed at necropsy.

Other findings:

None

Table 1: Signs of reaction to treatment

 

Signs of reaction	No. of rats in group of 1 * or 5 per sex showing signs
	Dose (mg/kg bw)
	3200*		5000
	Male	Female	Male	Female
Piloerection	1	1	5	5
Hunched posture	1	1	0	0
Pallid extremities	1	1	0	0
Increased salivation	1	1	5	5
Abnormal faeces^a	1	1	5	5
Ungroomed appearance^b	1	1	5	5

 

* Preliminary studies comprised one male and one female

a Characterised by soft to liquid faeces

b Characterised by soiled/stained fur around face/muzzle or ano/genital region or wet fur

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 for SR 9003 is greater than 5000 mg/kg bw in rats as no mortality was observed at this dose level.

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 401 and in compliance with GLP, groups (5/sex) of CD rats of Sprague Dawley origin [Hsd:Sprague-Dawley (CD)] were given a single oral dose of Propoxylated neopentylglycol diacrylate (SR 9003) at 5000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination. A preliminary study was also conducted on 1 rat/sex/dose at 3200 mg/kg bw and animals were observed for 7 days.

 

In the preliminary study, no mortality was observed. Piloerection, hunched posture, pallid extremities, increased salivation, abnormal faeces and ungroomed appearance seen in both rats. Bodyweight gain for both rats was considered satisfactory. No macroscopic abnormalities were observed in either animal at the terminal necropsy on Day 8. In the main study, no mortality was observed. Piloerection was observed in all rats within 4 minutes of dosing. This sign persisted and was accompanied in rats later on Day 1 and/or at later intervals during the study by increased salivation, abnormal faeces and ungroomed appearance, seen in all rats. There were no other signs of reaction to treatment and recovery was complete in all instances by Day 4. Bodyweight gain was considered satisfactory in all rats throughout the study. No macroscopic abnormalities were observed for animals killed at study termination on Day 15. In this study, the combined oral LD50 of Propoxylated neopentylglycol diacrylate (SR 9003) was considered to be greater than 5000 mg/kg bw.

  

The oral LD50 for Propoxylated neopentylglycol diacrylate (SR 9003) is greater than 5000 mg/kg bw in rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

McRae's study is a reliable study performed in accordance with OECD 401 guideline (klimisch score = 1).

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:

From February 17 to March 10, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

actual range of humidity was 12-14%; animal selection was not random

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 Laboratories, Portage, USA
- Age at study initiation: Approximately 56 days
- Weight at study initiation: 252-268 g (males) and 183-198 g (females)
- Housing: Individually housed in suspended, stainless steel, wire-mesh type cages
- Diet: Certified Rodent Chow® #5002 (PMI Nutrition International, Inc., St Louis, USA), ad libitum
- Water: Water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 65-71 °F
- Humidity: 31-51%
- Photoperiod: 12 h dark / 12 h fluorescent light

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: 52.1 L acrylic and stainless steel nose-only exposure chamber equipped with a stainless steel baffle
- Exposure chamber volume: 52.1 L
- Method of holding animals in test chamber: Animals were removed from their home cages and placed in the nose-only restraint tubes.
- Source and rate of air: Chamber air flow rate of 41 L/minute was supplied by the generation system.
- System of generating particulates/aerosols: Test article was metered from a reservoir through 0.125-inch Teflon® tubing by a liquid pump at a constant rate to an atomizer. The atomizer was operated with in-house compressed air at a pressure of 30 psig, resulting in airflow of 41 L/minute. The test article was atomized to produce a concentrated aerosol in a 4 L glass atomization chamber. Purge air (monitored by a flowmeter) was introduced into the atomization chamber to dilute and sweep the aerosol atmosphere into the exposure chamber.
- Method of particle size determination: Particle size distributions were determined each hour using a cascade impactor to determine the MMAD and GSD.
- Temperature and humidity in air chamber: 22-23 °C and 12-14%, respectively
- Chamber temperature, relative humidity and airflow were continuously monitored throughout the exposures and recorded every 30 minutes.

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric method: Chamber atmosphere samples for determination of the test article exposure level were collected at least hourly. The samples were withdrawn from the breathing zone of the test animals in the exposure chamber through glass fiber filters mounted open-faced in a filter holder. The test article concentration was calculated as the filter weight gain in mg divided by the volume of air sampled. The volume of air sampled was calculated as the sample flow rate multiplied by the sample duration.
- Nominal concentration: The amount of test article delivered by the generation system during the exposure was divided by the total volume of air passing through the chamber to give the nominal concentration.
- Samples taken from breathing zone: Yes
- Homogeneity: Samples were obtained prior to initiation of animal exposures to demonstrate that the test article was evenly distributed throughout the breathing zone of the animals.
- Food and water were not available to the animals during the exposure period. Following the required exposure duration, the animals were returned to their individual home cages where food and water were made available.
- Justification for route of administration and exposure levels: The inhalation route is one of the potential routes of human exposure to this test article and the 2 mg/L level was selected as per the regulatory requirement.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric method

Duration of exposure:

4 h

Concentrations:

- Nominal concentration: 3.1 mg/L; desired concentration: 2 mg/L ; analytical concentration: 2 ± 0.14 mg/L

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:
All animals were observed at least twice daily for morbidity, mortality, injury, and availability of food and water.
Clinical signs were conducted on all animals every 15 minutes during the first exposure hour, hourly for the remaining exposure duration, immediately on removal from the exposure system, at 1, 2 and 4 h post exposure and thereafter once daily for 14 days.
Body weights were recorded immediately prior to exposure (Day 1) and on Days 2, 3, 5, 8 and 15.
- Necropsy of survivors performed: Yes, all animals were killed by overdose of sodium pentobarbital at study termination. The trachea was exposed and clamped such that the lungs could be removed and examined in an inflated state. All major organs in the thoracic and abdominal cavities were observed for gross abnormalities.

Statistics:

No

Preliminary study:

None

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 2 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality was observed

Clinical signs:

other: - Signs of treatment during the exposure included labored breathing and increased activity. - During the 14 day post exposure period, signs of toxicity included wheezing, labored breathing, excessive lacrimation, rapid respiration, gasping, emaciated, red

Body weight:

- There was a minimal effect of the test article exposure on body weight gain.
- All animals temporarily lost weight after the exposure. However, recovery occurred overtime and achieved satisfactory body weight gain in all animals by the end of 14 day observation period.

Gross pathology:

- No macroscopic abnormalities were observed in any animal.

Other findings:

None

Table 1: Chamber exposure atmosphere monitoring

 

Group	Desired exposure concentration (mg/L)	Nominal exposure concentration (mg/L)	Test article exposure concentration (mg/L)
1	2	3.1	2.0 ± 0.14

 

Table 2: Chamber environment conditions

 

Group	Temperature (°C)	Relative humidity (%)	Chamber airflow (L/minute)
	Mean ± SD	Mean ± SD	Mean ± SD
1	23 ± 0.4	13 ± 0.6	41 ± 0

 

Table 3: Particle size distribution

 

Group	Hour	MMAD (µ)	GSD
1	1	3.51	1.40
	2	3.55	1.75
	3	3.47	1.99
	4	3.46	1.97

Table 4: Body weights

Group	Sex		Pre-exposure	Day 2	Day 3	Day 5	Day 8	Day 15
1	Male	Mean	257.4	240.2	248.5	275.2	310.2	369.2
		SD	6.1	10.5	13.5	10.5	12.8	17.3
	Female	Mean	190.2	167.7	161.5	176.0	204.4	235.1
		SD	6.1	16.7	24.7	25.5	20.3	18.0

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 for Propoxylated neopentylglycol diacrylate (Photomer® 4127) is greater than 2 mg/L (analytical) in rats.

Executive summary:

In an acute inhalation toxicity study (limit test) performed similarly to the OECD Guideline 403 and in compliance with GLP, groups (5/sex) of Sprague Dawley [Crl:CD® (BR)] rats were exposed to an aerosol atmosphere of a formulation of the Propoxylated neopentylglycol diacrylateP (Photomer® 4127) at concentration of 2 ± 0.14 mg/L air (analytical) for 4 h. Animals were then observed for mortality, clinical signs and bodyweight for 14 days and necropsy was performed in all animals for macroscopic examination.

No mortality was observed. Signs of treatment during the exposure included labored breathing and increased activity. During the 14 day post exposure period, signs of toxicity included wheezing, labored breathing, excessive lacrimation, rapid respiration, gasping, emaciated, red/brown material around the nose and mouth, red eyelids and body surface staining. Males returned to normal within 3 days post exposure and the females returned to normal within 6 days post exposure. There was a minimal effect of the test article exposure on body weight gain. All animals temporarily lost weight after the exposure. However, recovery occurred overtime and achieved satisfactory body weight gain in all animals by the end of 14 day observation period. No macroscopic findings were observed. In this study, the combined inhalational LC50 of Propoxylated neopentylglycol diacrylate (Photomer® 4127) was greater than 2 mg/L air (analytical).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

0.002 mg/m³ air

Quality of whole database:

Hilaski's study is a reliable study which is equivalent to the OECD 403 guideline (klimisch score = 1).

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:

14 June 2012 - 08 August 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

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: 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: the males had a mean body weight of 349 g (range: 346 g to 352 g) and the females had a mean body weight of 245 g (range: 237 g to 257 g)
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: the animals were acclimated to the study conditions for a period of 5 (females) or 8 (males) days before treatment.

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: 26 June 2012 to 13 July 2012.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure
- Washing: at 24h post-exposure, with a moistened cotton pad

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 20 mL/kg
- Constant volume: no.

Duration of exposure:

24 hours

Doses:

2000 mg/kg.

No. of animals per sex per dose:

5 animals per group.

Control animals:

no

Details on study design:

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

Statistics:

no

Sex:

male/female

Dose descriptor:

LD0

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 indicative of systemic toxicity were observed in any animals. Very slight or well-defined erythema was noted at application sites of all females and 4/5 males between days 2 and 8, except in one female for which moderate to severe erythe

Gross pathology:

No macroscopic test item-related findings were observed.
The macroscopic findings correlated with common histological findings in control rats, and thus were considered to be incidental.

Other findings:

no

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of the test item was higher than 2000 mg/kg in rats as no mortality occured as this dose level.

Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item following a single dermal application to rats.

This study was performed according to the international guidelines (OECD No. 402 and Council Regulation No. 440/2008 of 30 May 2008, Part B.3) and in compliance with the principles of Good Laboratory Practice.

 

Methods

The test item was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. From day 2, any local reactions at the treatment site were also noted. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. Macroscopic lesions were preserved in buffered formalin then destroyed at the finalization of the study report as no microscopic examination was performed.

Results

No unscheduled deaths and no clinical signs indicative of systemic toxicity were observed in any animals.

Very slight or well-defined erythema was noted at application sites of females and males between days 2 andsingle female had a more severe erythema on days 2 and 3 a  long with moderate edema and, until day 7, scabs. Various minor degrees of edema (days 2 to 5), dryness (days 3 to 9), and scabs (days 4 to 11) were also observed in a few other females and males.

When compared to CiToxLAB France historical control data, a lower body weight gain was noted in all males and females between day 1 and day 8. Their body weight gain returned to normal thereafter. The body weight of males was not affected by the test item treatment.

No macroscopic test item-related findings were observed.

 

Conclusion

The dermal LD50 of the test item was higher than 2000 mg/kg in rats.

Therefore, the test item is not classified as toxic or harmful by dermal route according to the criteria of CLP Regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Silvano's study is a reliable study performed in accordance with OECD 402 guideline (klimisch score = 1).

Additional information

Acute toxicity : via oral route

In an acute oral toxicity study (McRae 1998) performed according to OECD Guideline 401 and in compliance with GLP, groups (5/sex) of CD rats of Sprague Dawley origin [Hsd:Sprague-Dawley (CD)] were given a single oral dose of Propoxylated neopentylglycol diacrylate at 5000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination. A preliminary study was also conducted on 1 rat/sex/dose at 3200 mg/kg bw and animals were observed for 7 days.

In the preliminary study, no mortality was observed. Piloerection, hunched posture, pallid extremities, increased salivation, abnormal faeces and ungroomed appearance seen in both rats. Bodyweight gain for both rats was considered satisfactory. No macroscopic abnormalities were observed in either animal at the terminal necropsy on Day 8. In the main study, no mortality was observed. Piloerection was observed in all rats within 4 minutes of dosing. This sign persisted and was accompanied in rats later on Day 1 and/or at later intervals during the study by increased salivation, abnormal faeces and ungroomed appearance, seen in all rats. There were no other signs of reaction to treatment and recovery was complete in all instances by Day 4. Bodyweight gain was considered satisfactory in all rats throughout the study. No macroscopic abnormalities were observed for animals killed at study termination on Day 15. In this study, the combined oral LD50 of Propoxylated neopentylglycol diacrylate was considered to be greater than 5000 mg/kg bw.

 

Acute toxicity : via inhalation route

In an acute inhalation toxicity study (Hilaski 1999) performed similarly to the OECD Guideline 403 and in compliance with GLP, groups (5/sex) of Sprague Dawley [Crl:CD® (BR)] rats were exposed to an aerosol atmosphere of a formulation of the Propoxylated neopentylglycol diacrylate at concentration of 2 ± 0.14 mg/L air (analytical) for 4 h. Animals were then observed for mortality, clinical signs and bodyweight for 14 days and necropsy was performed in all animals for macroscopic examination.

No mortality was observed. Signs of treatment during the exposure included labored breathing and increased activity. During the 14 day post exposure period, signs of toxicity included wheezing, labored breathing, excessive lacrimation, rapid respiration, gasping, emaciated, red/brown material around the nose and mouth, red eyelids and body surface staining. Males returned to normal within 3 days post exposure and the females returned to normal within 6 days post exposure. There was a minimal effect of the test article exposure on body weight gain. All animals temporarily lost weight after the exposure. However, recovery occurred overtime and achieved satisfactory body weight gain in all animals by the end of 14 day observation period. No macroscopic findings were observed. In this study, the combined inhalational LC50 of Propoxylated neopentylglycol diacrylate was greater than 2 mg/L air (analytical).

 

Acute toxicity : via dermal route on rats (OECD 402)

The test item was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours. No unscheduled deaths and no clinical signs indicative of systemic toxicity were observed in any animals during the 14 -day observation period. Very slight or well-defined erythema was noted at application sites of females and males between days 2 and single female had a more severe erythema on days 2 and 3 a long with moderate edema and, until day 7, scabs. Various minor degrees of edema (days 2 to 5), dryness (days 3 to 9), and scabs (days 4 to 11) were also observed in a few other females and males. When compared to historical control data, a lower body weight gain was noted in all males and females between day 1 and day 8. Their body weight gain returned to normal thereafter. The body weight of males was not affected by the test item treatment. No macroscopic test item-related findings were observed.

The dermal LD50 of Propoxylated neopentylglycol diacrylate was higher than 2000 mg/kg bw in rats.

Justification for classification or non-classification

Based on the available data, no classification for acute toxicity is required for Propoxylated neopentylglycol diacrylate according to the Regulation (EC) No 1272/2008.

Justification for oral route : LD0> 5000 mg/kg bw.

Justification for inhalation : There is no mortality at 2 mg/L (maximal attainable concentration), and clinical signs were reversible in 7 days

Justification for dermal route: LD0> 2000 mg/kg bw.