Bis[bis(3,5,5-trimethylhexyl)dithiocarbamate-S,S']zinc

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13th Mar 2015 to 8th sept 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 7 th sept 2009

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis[bis(3,5,5-trimethylhexyl)dithiocarbamate-S,S']zinc

EC Number:

283-381-8

EC Name:

Bis[bis(3,5,5-trimethylhexyl)dithiocarbamate-S,S']zinc

Cas Number:

84604-96-6

Molecular formula:

C38H76N2S4Zn

IUPAC Name:

bis({[bis(3,5,5-trimethylhexyl)carbamothioyl]sulfanyl})zinc

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

technical trials ( batch no 204873134010)
Limit test ( batch no 204873154005)

Expiry date 25 Jan 2018
Purity >99%
off white powder
controlled temp storage 15-25°C, below 70 RH%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Number of animals: 14
Sex: 7 male and 7 female rats, the females were nulliparous
and non-pregnant.
Age and body weight (at dosing): Sighting exposures: 10 weeks old, 395 g and 413 g
(males) and 253 g and 256 g (females)
Main study (Group 2): 10 weeks old, 394-410 g
(males) and 227-244 g (females).
Randomization: Selected based on bodyweight prior to the exposure.
Acclimatization period: 22 days in the Sighting group and in the Main group 2

Source: Charles River Laboratories, Research Models and
Services, Germany GmbH, Sandhofer Weg 7, D-
97633 Sulzfeld
Hygienic level at arrival: SPF
Hygienic level during the study: Standard housing conditions
Justification of strain: Recognized by international guidelines as a
recommended test system.

Animal health: Only healthy animals were used for the test. The
health status was certified by the veterinarian.
Animal room: 522/6
Housing: Group of 5 (by sex) for main study; group of 2 for
sighting
Cage type: Type III polypropylene solid floor cages with stainless
steel mesh lids
Bedding: Lignocel Bedding for Laboratory Animals and
Arbocel nesting material were available to animals
during the study.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 19.0 - 20.9°C
Relative humidity: 32 – 68%
Ventilation: 15-20 air exchanges/hour

The animals were provided with ssniff SM R/M “Autoclavable Complete Feed for Rats
and Mice – Breeding and Maintenance” (ssniff Spezialdiäten GmbH, D-59494 Soest
Germany; batch: 575 4308; expiry: March 2016, 540 5117; expiry: July 2016) and tap
water fit for human consumption, ad libitum.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: technical trials of powder alone failed to generate required atmospheric concentration, acetone was successful

Remarks:

acetone was used to aerosolise and overcome the low mpt solid issues in test system

Mass median aerodynamic diameter (MMAD):

ca. 2.36 - ca. 2.38 µm

Geometric standard deviation (GSD):

ca. 2.46 - ca. 2.57

Remark on MMAD/GSD:

inhalable fraction- ( % less than rat inhalable fraction 4μm) was 70.8%

Details on inhalation exposure:

Group 1 sighting study
Maximum attainable Atmosphere Concentration = 4.97 mg/L
Standard Deviation = 0.38
Nominal Concentration:
Amount of Test Item Used (g): 153.82
Total Volume of Air Used (L): 7560
Nominal Concentration = 20.35 mg/L

Atomsophere analysed 17 times during study.

Group 2
Maximum attainable Atmosphere Concentration = 5.04 mg/L
Standard Deviation = 0.23
Nominal Concentration:
Amount of Test Item Used (g): 135.55
Total Volume of Air Used (L): 7530
Nominal Concentration = 18.00 mg/L

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

>= 4 h

Concentrations:

Group 2
Maximum attainable Atmosphere Concentration = 5.04 mg/L
Standard Deviation = 0.23

Control animals:

no

Remarks:

acetone was used a below level of toxicity

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:


- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

>= 5.04 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

no mortality seen in sighting study ( group 0.1)
no mortality seen in group 1 ( technical reasons this was abandoned)
no mortality seen in group 2 ( successfully completed limit test)

Clinical signs:

other: Sighting group (Group 0.1): Laboured respiration (slight to moderate), respiratory rate increased (slight), activity decreased (slight to moderate), incoordination (slight to moderate) were observed on the day of exposure. The animals were symptom free fr

Body weight:

The exposure procedure caused slight bodyweight loss in the animals (0.8 %-9.0 %). After
the exposure normal body weight gain was observed.

Gross pathology:

A single four hours nose-only exposure of Arbestab Z to Crl:WI rats exposed to the
concentration of 4.97 mg/L during Sighting exposure and 5.04 mg/L during Main study, was
not associated with any test item-related gross changes.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, no deaths occurred in a group of ten
rats exposed to the concentration of 5.04 mg/L for four hours. The acute inhalation
median lethal concentration (4hr LC50) of Arbestab Z, in CRL: (WI) Wistar strain
rats, was therefore considered to be greater than 5.04 mg/L.