1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (90-Day (Subchronic) Inhalation Toxicity Study

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

EC Number:

262-104-4

EC Name:

1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

Cas Number:

60207-90-1

Molecular formula:

C15H17Cl2N3O2

IUPAC Name:

1-{[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl}-1H-1,2,4-triazole

Test animals

Species:

rat

Strain:

other: RAIf SPF

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

head only

Vehicle:

other: Acetone

Duration of treatment / exposure:

6 hours/day

Frequency of treatment:

5 days per week for 13 weeks

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

20 mg/m³ air (nominal)

Remarks:

21 mg/m3 air (actual concentration)

Doses / concentrations 2

Dose / conc.:

80 mg/m³ air (nominal)

Remarks:

85 mg/m3 air (actual concentration)

Doses / concentrations 3

Dose / conc.:

200 mg/m³ air (nominal)

Remarks:

191 mg/m3 air (actual concentration)

Control animals:

yes, sham-exposed

Results and discussion

Effect levels

Dose descriptor:

NOEC

Effect level:

20 mg/m³ air (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

body weight and weight gain

histopathology: non-neoplastic

Remarks on result:

other: Equivalent to 21 mg/m3 air (acutal dose received)

Target system / organ toxicity

Critical effects observed:

no

Any other information on results incl. tables

Table 1. Summary of study test atmosphere characteristics

Parameter
Group	Negative control	Vehicle control	Exposure level
Gravimetric concentration	0 (air)	10 mg/m3 acetone	21±2 mg/m3	85±7 mg/m3	191±10 mg/m3
Particle size distribution	>80% smaller than 7 µm
Air flow (m/sec)	0.4	0.41	0.4	0.4	0.41
Temperature (°C)	24.8	24.9	24.8	24.9	24.9
Humidity (%)	63.9	66.3	66.3	65.9	64.5
Oxygen content (%)	20.3	20.4	20.4	20.3	20.2

Mortality: There were no treatment related mortalities.
Clinical observations: No clinical symptoms and no signs of local and/or systemic toxicity were observed.
Body weight and gain: Slightly lower body weights in the males at 85±7 mg/m3 and females at 21±2 and 191±10 mg/m3 were seen on some occasions during the treatment period achieving statistical significance (p≤0.01) when compared with the controls.

Table 2. Intergroup comparison of mean body weight (g)

Study week		Males				Females
	Negative control	Vehicle control	Exposure level			Negative control	Vehicle control	Exposure level
	0 (air)	10 mg/m3 acetone	21±2 mg/m3	85±7 mg/m3	191±10 mg/m3	0 (air)	10 mg/m3 acetone	21±2 mg/m3	85±7 mg/m3	191±10 mg/m3
1	227	232	222	222	216	186	192	184	191	184
2	259	262	251	249	245	199	205	189	196	193
3	292	293	284	278	279	211	214	200	203	201
4	319	318	309	229*	302	222	229	209*	212	209*
5	319	33	327	319	321	228	236	212*	219	215*
6	332	335	331	321	328	236	239	219*	225	217*
7	354	356	349	336*	349	240	247	225*	229	226*
8	371	367	361	347*	358	246	249	228*	236	227*
9	387	390	380	366*	379	250	257	232*	243	234*
10	401	413	396	385	399	254	268*	242	251	240
11	417	429	417	401	413	260	273*	248	253	246*
12	429	434	430	414	427	263	274	249*	258	250
13	433	448	446	425	439	265	273	250*	258	249*

* Statistically significant difference from control group mean (p≤0.01).

Food consumption and utilisation: No effect on food consumption or food utilisation was noted.
Food consumption and compound intake: The mean food consumption of all treated male and female rats was comparable to the controls.
Ophthalmoscopic examination: No treatment related effects noted.
Haematology: There were no differences in haematological parameters which were considered to be related to treatment.
Blood clinical chemistry: There were no differences in blood clinical chemistry parameters which were considered to be related to treatment.

Sacrifice and pathology:
Organ weights: Some organ weight, organ to body weight and organ to brain weight ratios showed some intra-group variation, but none were considered to be toxicologically significant.
Macroscopic findings: There were no treatment related macroscopic abnormalities.
Microscopic findings: There were no treatment related microscopic abnormalities.

Applicant's summary and conclusion

Conclusions:

A NOEC of the test substance for male rats was established at 20 mg/m3 (21 mg/m3 acutal dose received) but not for females because of the body weight differences noted at this exposure level.

Executive summary:

In this inhalation toxicity study, test substance was administered by aerosol exposure (to the head only) to groups of 20 male and 20 female RAIf SPF rats at dose levels of 0 (air), 10 (acetone, vehicle control), 21±2, 85±7 or 191±10 mg/m3 for 6 hours per day, 5 days per week for a period of 90 days.Test atmospheres were analysed daily for particulate concentration and test substance. Mortality, clinical observations, body weights and food consumption were measured throughout the study. Blood samples were collected from 10 fasted rats per sex per group at 6 and 13 weeks for haematology and clinical chemistry analysis. Brain, heart, liver, lungs and kidneys were weighed. A comprehensive range of organs and tissues from all animals was examined histopathologically.
There were no treatment related mortalities. No clinical symptoms and no signs of local and/or systemic toxicity were observed. No effects on food consumption or food utilisation were noted. Slightly lower body weights in the males at 85±7 mg/m3and in females at 21±2 mg/m3 and 191±10 mg/m3 were seen on some occasions during the treatment period when compared with the controls. The results of the haematological investigation and blood chemistry data were generally unremarkable for both treated rats and controls. There were no treatment related macroscopic or microscopic changes. Some organ weight, organ to body weight and organ to brain weight ratios showed some intra-group variation, but none were considered to be toxicologically significant.

A NOEC of test substance technical for male rats was established at 21 mg/m3 but not for females because of the body weight differences noted at this exposure level.