Bis(2-ethylhexyl) phthalate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

lack of informtation on materials, animals

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) phthalate

EC Number:

204-211-0

EC Name:

Bis(2-ethylhexyl) phthalate

Cas Number:

117-81-7

Molecular formula:

C24H38O4

IUPAC Name:

1,2-bis(2-ethylhexyl) benzene-1,2-dicarboxylate

Details on test material:

Name of test material (as cited in study report): Vestinol AH as supplied by the sponsor
Purity: not indicated
Physical state: clear colourless liquid
Storage: in its original container under ambient conditions

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 (UK) Limited, Manston, Kent
- Age at study initiation: approx. 6 weeks old
- Weight at study initiation: between 120 and 150 g
- Fasting period before study: no
- Housing: 5/cage (sexes being kept separated)
- Diet (e.g. ad libitum): ad libitum BP Nutrition Diet N°1 laboratory small animal diet
- Water (e.g. ad libitum): ad libitum tap water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2
- Humidity (%): 50 (40-63)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The test atmospheres were generated by means of continuously metering Vestinol AH from a Sage motorised syringe pump through a glass concentric jet atomiser operating with an air flow rate of approximately 7.0 l/min. The concentration within the exposure chamber was altered by adjusting the speed of the syringe pump, and/or varying the volume of dilution air flowing into the chamber.

Compressed air was supplied by means of 2 Broomwade compressors (Type CAR 31) fitted with automatic pressure control switches. These supplied filtered, conditioned, oil-free compressed air for subsequent dilution of test atmospheres.

The exposure chamber was cylindrical in cross section and constructed of aluminium. It had a volume of approximately 41.5 L and was fitted with a flat top which supported the syringe driver. An extract duct in the base was connected by way of a high efficiency filter to a metered vacuum system. The exposure chamber was mounted inside an extract cabinet for the protection of operators and the environment.

Each rat was held in an individual, tapered, polycarbonate restraint tube. Each tube was fitted onto the exposure chamber and sealed by means of a push fit through a rubber 'o' ring. All the animals were exposed on a single tier eliminating exposure variation, only the animals' noses being exposed to the test atmosphere. The temperature within the exposure chamber was maintained at 21°C + 2°C.

The exposure system was truly dynamic incorporating a single pass of the freshly generated material. The particles dispersed evenly throughout the chamber and exited through a series of small holes connected to a filtered vacuum line operating at a flow rate of approximately 2 1/min greater than the input flow rate, therefore reducing risk of contamination of the environment.

The control group of animals was subjected to the same conditions and manipulations as the test animals with the exception that clean compressed air alone was passed through the chamber.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

3.39, 6.82, or 10.62 mg/l

No. of animals per sex per dose:

5 males and 5 females (total of 45 males and 45 females)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
During the subsequent 14-day observation period the rats were inspected twice daily.
Body weights were measured before exposure and on days 2, 3, 4, 7, 10 and 14 post-exposure.
- Necropsy of survivors performed: yes
- Other examinations performed:
Food consumption was visually assessed daily.
A detailed macroscopic examination was performed on all animals at sacrifice at the end of the observation period.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 10 620 mg/m³ air (nominal)

Mortality:

No animals died during or after the exposure.

Clinical signs:

other: The behaviour of the control animals during exposure was considered to be normal. After an initial 5-10 min period of struggling and increased urination and defecation the animals became settled. Occasional red smears around the eyes were observed where t

Body weight:

Body Weight gain was considered to be normal for control animals and those dosed with 3.39 and 6.82 mg/1 Vestinol AH. Animals dosed with 10.62 mg/1 showed a loss/reduced body weight gain on day 2 post-exposure. Resumption of normal body weight gain was observed from day 3 onwards.

Gross pathology:

In all groups, dark red foci and patches were observed in the lungs at post mortem inspection. These findings were more frequent in the treated animals.

Other findings:

- Food and water consumption were estimated visually. No differences between control and treated animals were observed.
- The particle size distribution indicated a respirable fraction of 62.8, 57.0 and 48.5% respectively for test groups 2, 3 and 4.
- Pathological examination at post mortem revealed the presence of dark red foci and patches in the lungs. These foci and patches were observed more frequently in the treated animals than in controls.
Control: 2/10
Vestinol AH: 19/30
N°7 male showed extensive red areas in the hilar regions of the lungs.
N°33 female had dark red, enlarged lungs, with areas of white in ail lobes. This is considered to have occurred during autopsy and was probably due to some blood entering the lung.
The lung/body weight ratios of all treated groups were similar to the ratios obtained in the control group. The increased lung weight (2.29 g) recorded for N°33 female resulted in an extremely high lung/body weight ratio and has not been included in the Group 2 mean value. All other values were considered to be within normal limits.

Any other information on results incl. tables

Determination of Acute Inhalation Toxicity (LC50} in the Rat Exposure Chamber Concentrations of Vestinol AH
Group/Generator Setting	Time of Sample {mins)	Nett Weight of Sample (mg)	Volume of Air Sampled (l)	Exposure Chamber concentration (mg/l)
2 Pump: 0.7 ml/min Aerosol Air: 7.0 l/min Dilution Air: 10.0 l/min	25	123.0	27.5	4.47
	90	62.3	27.5	2.27
	110	65.6	27.5	2.39
	180	74.3	27.5	2.70
	230	70.1	13.75	5.10
				Mean 3.39
3 Pump: 1.7 ml/min Aerosol Air: 7.0 l/min Dilution Air: 0.0 l/min	40	81.9	25.0	3.28
	110	109.7	12.5	8.78
	180	85.2	12.5	6.82
	210	105.1	12.5	8.41
				Mean 6.82
4 Pump: 3.1 mm/min Aerosol Air: 7.0 l/min	45	106.7	12.5	8.54
	80	215.3	17.5	12.30
	175	143.6	12.5	11.50
	205	126.8	12.5	10.14
				Mean 10.62

Group	Sex	Observation period days	Predose	2	3	4	7	10	14
1	Male	Mean	173.4	183.8	195.4	201.6	223.6	244.4	272.8
		+S.D.	7.2	8.7	8.0	7.7	9.5	11.5	18.2
	Female	Mean	168.6	172.2	184.0	189,8	200.4	210.2	223.8
		+3.0.	5.5	4.2	6.2	6.6	6.9	10.9	12.9
2	Male	Mean	179.6	192.6	207.0	212,2	235.8	255.6	284.8
		+S.D.	3.8	6.3	7.7	7.6	- 9.3	12.7	20.9
	Female	Mean	166.4	173.4	182.0	185.2	193.6	206.8	222.2
		±9.D,	7.1	8.5	9.4	6.0	8.8	8.9	12.2
3	Male	Mean	181.0	188.4	196.2	202.0	221.6	246,2	273.2
		+S.D.	11.6	15.4	14.3	16.0	16.3	17.1	20.6
	Female	Mean	165.8	173.8	179.4	179.8	190.6	205.8	218.6
		+S.D.	14.0	12.9	14.6	15.9	18.1	19.6	20.3
4	Male	Mean	209.0	203.6	213.4	226.6	242.0	260.8	283.0
		+S.D.	5.2	2.3	5.2	5.8	-8.1	11.2	8.8
	Female	Mean	175.6	176.8	184.0	188.8	195.4	206.4	214.4
		+S.D.	9.6	9.5	10.4	12.0	10.4	11.4	12.1

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008

Conclusions:

The LC0 of DEHP via inhalation was in this study found to be in excess of 10,620 mg/m3 for 4 hours

Executive summary:

In a study performed according to GLP principles, groups of 5 male and 5 female rats were exposed for 4 hours to clean air (control group) or DEHP (purity not specified) in concentrations of either 3.39, 6.82, or 10.62 mg/litre (3,390, 6,280, or 10,620 mg/m3). The highest dose was considered the technical limit of aerosol generation for the test material. The control group and the lowest dose group were exposed on the same day. The mid-dose group and the highest dose group were exposed on different days. The exposure was nose-only. The rats were observed for clinical signs throughout the exposure period and for the first 4 hours after dosing. During the subsequent 14-day observation period the rats were inspected twice daily. Body weights were measured before exposure and with regular intervals during the observation period. A detailed macroscopic examination was performed on all animals at sacrifice at the end of the observation period. No animals died during or after the exposure. All treated animals showed a slightly unkempt appearance for 1-2 days after exposure, those in the highest dose group had a yellowish staining on their fur. This group also had a reduced body weight gain on the second day after exposure, which subsequently returned to the normal pattern. In all groups, dark red foci and patches were observed in the lungs at post mortem inspection. These findings were more frequent in the treated animals. In conclusion, the LC0 of DEHP via inhalation was in this study found to be in excess of 10,620 mg/m3 for 4 hours.