Hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, <5% n-hexane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 Mar 1999 - 02 Apr 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Principles of method if other than guideline:

Animals were exposed to the test atmosphere and checked for health, viability and clinical signs.

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspectorate for Health Protection, Commodities and Veterinary Public Health, Ministry of Health, Welfare and Sport

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, <5% n-hexane

EC Number:

921-024-6

Molecular formula:

none available - not a single isomer - see remarks

IUPAC Name:

Hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, <5% n-hexane

Details on test material:

- Name of test material (as cited in study report): Cypar 7 supplied by Hanf + Nelles, Düsseldorf, Germany
- Physical state: clear, volatile liquid
- Analytical purity: 100% pure commercial product
- Lot/batch No.: 97 H 5 S
- Storage condition of test material: ambient temperatures, in the dark

Test animals

Species:

rat

Strain:

other: WAG/RijCrlBR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 14 weeks
- Weight at study initiation: approximately 250 g at randomization

- Housing: Prior to randomization, the animals were housed in groups of 5 in suspended stainless steel cages. After randomization animals were housed individually in wire-mesh cages. The animals were acclimatized to the exposure chambers 5 days prior to the pre-exposure test.
- Diet (ad libitum): commercial rodent diet (Rat & Mouse No. 3 Breeding Diet, RM3)
- Water (ad libitum): Tap water suitable for human consumption (quality guidelines according to Dutch legislation based on EEC Council Directive 80/778/EEC, see Annex 3) was supplied by N.V. Waterleidingbedrijf Midden-Nederland (WMN).
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 and in exposure chambers: 20-25
- Humidity (%): 30-62 and in exposure chambers: 32-66 (minimum 28)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): artificially illuminated for 12 hours between 07:00 a.m. to 07:00 p.m.


IN-LIFE DATES: From: 1999-03-10 To: 1999-04-02

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: air

Remarks on MMAD:

MMAD / GSD: no data

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: modified H 1000 inhalation chambers (Hazleton Systems Inc., USA)
Each chamber had a pyramidal top and bottom and was constructed of stainless steel with glass doors on two sides.
- System of generating particulates/aerosols: test atmosphere was generated by pumping liquid Cypar 7 into stainless steel tubing using peristaltic pumps (Watson and Marlowe).
- Temperature, humidity in air chamber: 20-25 °C, 32-66 (minimum 28) %
- Air flow rate: 11.9 m3/h (results from earlier experiments)



TEST ATMOSPHERE
- Brief description of analytical method used: During exposure a total carbon analyzer (TCA, Ratfisch, Germany) was operated with 4 ports which weresuccessively sampled during 7 minutes. The ports were connected to exposure chamber A (control), B (lower concentration), C (mid concentration) and D (higher concentration). The TCA readings were calibrated using PET sample bags filled with 50 l air and Cypar 7 corresponding to concentrations of 1.22, 4.27, and 15.25 g/m3.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

During exposure a total carbon analyzer (TCA) was operated with 4 ports for control and 3 test concentrations. Shortly after the experiment, a stability check of the TCA was performed using two PET sample bags prepared at 14 g/m3, the highest concentration used.

Duration of treatment / exposure:

8 hours

Frequency of treatment:

once daily for 3 consecutive days

Doses / concentrations

Remarks:

Doses / Concentrations:
0 g/m3; 1.4 g/m3 corresponding to 305 ppm; 4.2 g/m3 corresponding to 915 ppm; 14 g/m3 corresponding to 3050 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

8

Control animals:

yes, concurrent vehicle

Details on study design:

- Rationale for animal assignment: The rat was selected because this species is considered suitable for this type of study and was the species specified in the TNO EZ Collective project proposal. The strain of rats used in these experiments has been used extensively in behavioral studies within TNO.

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least once daily
- Cage side observations checked: no details given


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: prior to randomization (no details given)


BODY WEIGHT: Yes
- Time schedule for examinations: body weight was recorded during randomization and on days of testing

Statistics:

All data were analyzed using the SAS® statistical software package (release 6.12). For each test measure, probability values of p≤0.05 were consideredsignificant.Treatment effects were analyzed using repeated measures analysis of variance. Group comparisons were made using Dunnett´s multiple comparison tests.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Behaviour (functional findings):

effects observed, treatment-related

Details on results:

Exposure levels used in this study were sufficiently high to induce signs of general intoxication.

CLINICAL SIGNS AND MORTALITY
One animal from the 4.2 g Cypar 7/m3 group kept its head bend with the left side directed towards the ground.


BODY WEIGHT AND WEIGHT GAIN
Slightly decreased body weights in animals from the 14 g Cypar 7/m3 group after the 3-day exposure period indicated Cypar 7-induced toxicity in these animals. In addition, body temperature was decreased in the 14 g Cypar/m3 group after both the first and the third exposure period.

Effect levels

Key result

Dose descriptor:

NOAEC

Effect level:

14 000 mg/m³ air (nominal)

Sex:

male

Basis for effect level:

other: non-persistent neurobehavioral effects on learned performance

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In conclusion, short-term high-level exposure to hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, <5% n-hexane up to and including 4200 mg/m3 did not induce effects related to general toxicity.

Executive summary:

In conclusion, short-term high-level exposure to hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, <5% n-hexane up to and including 4200 mg/m3 did not induce effects related to general toxicity.