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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Esterification products of acrylic acid with reaction products of 2,2-dimethylpropane-1,3-diol and methyloxirane
EC Number:
701-440-2
Molecular formula:
(C3H6O)x (C3H6O)y C11H16O4
IUPAC Name:
Esterification products of acrylic acid with reaction products of 2,2-dimethylpropane-1,3-diol and methyloxirane
Test material form:
liquid

Test animals

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

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: 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

Results and discussion

Preliminary study:
None
Effect levels
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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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).